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The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer

October 2013
European Journal of Nuclear Medicine and Molecular Imaging 41(6)

DOI:10.1007/s00259-013-2544-2

Source
PubMed

Authors:

Francesco Giammarile

International Atomic Energy Agency (IAEA)

Naomi Alazraki

Emory University

John N. Aarsvold

Emory University

Riccardo A Audisio

University of Gothenburg

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The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, surgical oncology and pathology. The aim of this document is to provide general information about sentinel lymph node detection in breast cancer patients. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM) have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. The final result has been discussed by distinguished experts from the EANM Oncology Committee, the SNMMI and the European Society of Surgical Oncology (ESSO). The present guidelines for nuclear medicine practitioners offer assistance in optimizing the diagnostic information from the SLN procedure. These guidelines describe protocols currently used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

Recommendations regarding use of SLN biopsy

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Characteristics of 99m Tc-based radiopharmaceuticals

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Ranges of estimates of radiation exposures

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GUIDELINES

The EANM and SNMMI practice guideline for lymphoscintigraphy

and sentinel node localization in breast cancer

Francesco Giammarile &Naomi Alazraki &John N. Aarsvold &Riccardo A. Audisio &

Edwin Glass &Sandra F. Grant &Jolanta Kunikowska &Marjut Leidenius &

Vale r i a M . M o n c a yo &Roger F. Uren &Wim J. G. Oyen &Renato A. Valdés Olmos &

Sergi Vidal Sicart

Received: 8 August 2013 /Accepted: 13 August 2013

#EANM 2013

Abstract

Purpose The accurate harvesting of a sentinel node in breast

cancer includes a sequence of procedures with components

from different medical specialities, including nuclear medi-

cine, radiology, surgical oncology and pathology. The aim of

this document is to provide general information about sentinel

lymph node detection in breast cancer patients.

Methods The Society of Nuclear Medicine and Molecular

Imaging (SNMMI) and the European Association of Nuclear

Medicine (EANM) have written and approved these guide-

lines to promote the use of nuclear medicine procedures with

high quality. The final result has been discussed by

distinguished experts from the EANM Oncology Committee,

the SNMMI and the European Society of Surgical Oncology

(ESSO).

Conclusion The present guidelines for nuclear medicine

practitioners offer assistance in optimizing the diagnostic

information from the SLN procedure. These guidelines

describe protocols currently used routinely, but do not

include all existing procedures. They should therefore

not be taken as exclusive of other nuclear medicine

modalities that can be used to obtain comparable re-

sults. It is important to remember that the resources and

facilities available for patient care may vary.

F. Giammarile (*)

Médecine Nucléaire, Hospices Civils de Lyon and EA 3738,

Université Claude Bernard Lyon 1, Lyon, France

e-mail: francesco.giammarile@chu-lyon.fr

N. Alazraki :J. N. Aarsvold :S. F. Grant

Nuclear Medicine Service Veterans Affairs Medical Center and

Department of Radiology and Imaging Sciences, Emory University,

Atlanta, GA, USA

R. A. Audisio

St Helens Teaching Hospital, University of Liverpool, St Helens, UK

E. Glass

Nuclear Medicine, Medical Imaging Center of Southern California,

Santa Monica, CA, USA

J. Kunikowska

Nuclear Medicine Department, Medical University of Warsaw,

Warsaw, Poland

M. Leidenius

Breast Surgery Unit, Helsinki University Central Hospital, Helsinki,

Finland

V. M. Moncayo

Nuclear Medicine Service, Emory University, Atlanta, GA, USA

R. F. Uren

University of Sydney, Sydney, NSW, Australia

R. F. Uren

Nuclear Medicine and Diagnostic Ultrasound, RPAH Medical

Centre, Suite 206, Newtown, NSW, Australia

W. J. G. Oyen

Department of Nuclear Medicine, Radboud University Nijmegen

Medical Centre, Nijmegen, The Netherlands

R. A. Valdés Olmos

Department of Nuclear Medicine, Netherlands Cancer Institute,

Amsterdam, The Netherlands

R. A. Valdés Olmos

Interventional Molecular Imaging, Leiden University Medical

Center, Leiden, The Netherlands

S. Vidal Sicart

Nuclear Medicine Department, Hospital Clinic Barcelona,

Barcelona, Spain

Eur J Nucl Med Mol Imaging

DOI 10.1007/s00259-013-2544-2

Keywords Sentinelnode .Breast cancer .Lymphoscintigraphy .

Blue dye .Gamma probe .Gamma camera

Preamble

The Society of Nuclear Medicine and Molecular Imaging

(SNMMI) and the European Association of Nuclear Medicine

(EANM) have written and approved guidelines to promote the

use of nuclear medicine procedures with high quality. These

guidelines are intended to assist practitioners in providing

appropriate nuclear medicine care for patients. They are not

inflexible rules or requirements of practice and are not

intended, nor should they be used, to establish a legal standard

of care. For these reasons and those set forth below, the

SNMMI and EANM caution against the use of these guide-

lines in litigation in which the clinical decisions of a practi-

tioner are called into question.

The ultimate judgment regarding the propriety of any spe-

cific procedure or course of action must be made by medical

professionals taking into account the unique circumstances of

each case. Thus, an approach that differs from the guidelines

does not necessarily imply that the approach was below the

standard of care. To the contrary, a conscientious practitioner

may responsibly adopt a course of action different from that

set forth in the guidelines when, in the reasonable judgment of

the practitioner, such course of action is indicated by the

condition of the patient, limitations of available resources, or

advances in knowledge or technology subsequent to publica-

tion of the guidelines.

The practice of medicine involves not only the science, but

also the art of dealing with the prevention, diagnosis, allevia-

tion, and treatment of disease. The variety and complexity of

human conditions make it impossible at times to identify the

most appropriate diagnosis or to predict with certainty a

particular response to treatment. Therefore, it should be rec-

ognized that adherence to these guidelines will not assure an

accurate diagnosis or a successful outcome. All that should be

expected is that the practitioner will follow a reasonable

course of action based on current knowledge, available re-

sources, and the needs of the patient to deliver effective and

safe medical care. The sole purpose of these guidelines is to

assist practitioners in achieving this objective.

Introduction

The accurate harvesting of a sentinel node in breast cancer

includes a sequence of procedures with components from

different medical specialities, including nuclear medicine,

radiology, surgical oncology, and pathology. The topics cov-

ered are presented under the headings: Goals;Background and

Definitions;Common Clinical Indications and Precautions;

Qualifications and Responsibilities of Personnel;Procedures in

Nuclear Medicine;Procedures in the Surgical Suite;Radiation

Dosimetry;andIssues Requiring Further Clarification.

The present guideline has been prepared for nuclear med-

icine practitioners. The intent is to offer assistance in optimiz-

ing the diagnostic information that can be obtained from

sentinel lymph node (SLN) procedures. If specific recommen-

dations given cannot be based on evidence from original

scientific studies, referral is made to “general consensus”

and similar expressions. The recommendations are designed

to assist in the referral, performance, interpretation, and

reporting of the SLN procedure.

Goals

The aim of this document is to provide general information

about SLN detection in breast cancer patients. This guideline

describes protocols currently used routinely, but does not

include all existing procedures. It should therefore not be

taken as exclusive of other nuclear medicine modalities that

can be used to obtain comparable results. It is important to

remember that the resources and facilities available for patient

care may vary. The present guideline for nuclear medicine

practitioners offers assistance in optimizing the diagnostic

information from the SLN procedure. The final result has

been discussed by distinguished experts from the EANM

Oncology Committee, the SNMMI, and the European Society

of Surgical Oncology (ESSO).

Background and def initions

Breast cancer is the most frequent cancer diagnosed in women

worldwide [1]. SLNs are the regional nodes that directly drain

lymph from the primary tumour. Thus, SLNs are the first

nodes to receive lymph-borne metastatic cells [2]. After the

description by Morton et al. of a method for SLN biopsy in the

management of melanoma patients [3] two decades ago, SLN

mapping and biopsy have been used in breast cancer [4]. Since

then, SLN mapping and biopsy have become routine tech-

niques in breast cancer management, contributing to the de-

velopment of less-invasive surgical procedures [4–12].

Accurate lymph node staging is essential for both progno-

sis (of early-stage disease) and treatment (for regional control

of disease) in patients with breast cancer. Lymphoscintigraphy

(LS) allows the surgeon to easily identify and biopsy a SLN.

No imaging modality is accurate enough to detect lymph node

metastases when a primary breast cancer is at an early stage

(I or II), but SLN biopsy is a highly reliable method for

screening axillary nodes and for identifying metastatic and

micrometastatic disease in regional lymphatic nodes [12–14].

Eur J Nucl Med Mol Imaging

Despite the widespread use of SLN biopsy for early-stage

breast cancer, there is significant variation in performance

characteristics reported for the procedure. Differences in study

volumes and in lymphatic mapping techniques are two of the

factors contributing to variations in the proportions of suc-

cessful mappings [15]. The ranges of rates for false-negative

findings and for SLN identifications emphasize the variability

of this procedure. Learning curves for this technical procedure

also vary [15]. Nevertheless, once a multidisciplinary team is

experienced with the procedure, reasonable levels of accuracy

are achieved, with identification rates of more than 95 %

reported routinely [16].

Common clinical indications and precautions

Indications for a SLN procedure include, but are not limited

to, those in the following discussion. Table 1is a list of several

indications, together with recommendations as to whether a

SLN procedure is established standard care.

Common indications

SLN localization and biopsy are now the “standard of care”

for staging the axillary lymph nodes in breast cancer patients.

These procedures have replaced routine staging axillary

lymph node dissection (ALND) in patients with early-stage

biopsy-proven breast carcinoma without cytologically or his-

tologically proven axillary lymph node metastases [17,18].

ALND is a standard treatment for patients with axillary

metastases identified on SLN procedures. ALND is also an

often-used option in the management of patients in whom a

SLN is not identified intraoperatively, but what should be the

standard care in such patients is unresolved. A treatment

alternative in patients with metastatic axillary SLNs is axillary

radiotherapy. These two treatment options (ALND and radio-

therapy) are being compared in the EORTC AMAROS trial

(ongoing) [19]. A concern regarding these patients arises from

data suggesting fewer than 40 % of those with positive axil-

lary SLNs have non-sentinel nodes with metastases [20].

Investigations to identify risk factors for non-sentinel node

metastases have been conducted with the goal of identifying a

subgroup in whom ALND could be omitted despite metastatic

findings in axillary SLNs. The identified risk factors can be

combined and normograms created to evaluate the risk of

residual disease in the axilla [21–23]. Another concern regard-

ing these patients arises from data obtained in a recent ran-

domized study in which it was concluded ALND provides

no advantage in SLN-positive patients with breast-

conserving surgery and whole-breast radiotherapy [24,

25]. However, patients with micrometastases were over-

represented in this study, especially in the arm without

ALND [25]. Also, the follow-up was too short to draw

definitive conclusions regarding survival. Nevertheless, re-

sults suggest the majority of SLN-positive patients may

not benefit from ALND [26–28].

Patients with negative axillary SLN biopsy by routine

histopathological evaluation do not require ALND. The clin-

ical significance of isolated tumour cells detected by immu-

nohistochemistry is currently controversial [29]. Neither the St

Gallen nor the American Society of Clinical Oncology

(ASCO) guidelines recommend ALND in patients with iso-

lated tumour cells in their SLNs [30–32].

Axillary SLN biopsy procedures are now preferred to

ALND for routine axillary staging in early breast cancer [14,

30–34] in many if not most clinical scenarios, as detailed in

Tab le 1and in guidelines of the ASCO [32]. In these patients,

SLN biopsy has a positive node rate similar to that observed in

patients who have axillary lymphadenectomy [14,35]. SLN

biopsy has significantly lower morbidity than axillary lymph-

adenectomy [36], and it has nodal relapse rates at 5 years similar

to those of axillary lymphadenectomy [37]. No significant

differences in disease-free survival, overall survival, or local

control of disease have been seen with a negative SLN [35].

Tabl e 1 Recommendations regarding use of SLN biopsy

Clinical circumstance Use of SLN biopsy

T1 or T2 tumour Established

T3 or T4 tumour Controversial (see “T3 and T4 tumours”)

Multicentric or

multifocal tumour

Controversial (see “Multifocal and

multicentric tumours”)

Inflammatory breast cancer Not recommended

DCIS with mastectomy Established (see “Ductal carcinoma in situ”)

DCIS without mastectomy Controversial, except for DCIS with

suspected or proven microinvasion

(see “Ductal carcinoma in situ”)

Suspicious, palpable

axillary nodes

Controversial (see “Suspicious palpable

nodes”)

Older age Established

Obesity Established

Male breast cancer Established

Pregnancy Controversial (see “Precautions”)

Evaluation of internal

mammary lymph nodes

Controversial (see “Evaluation of internal

mammary and other extra-axillary nodes”)

Prior diagnostic or

excisional breast biopsy

Controversial (see “Prior breast surgery

other than excisional biopsy”)

Prior axillary surgery Controversial (see “Prior axillary surgery”)

Prior nononcological breast

surgery

Controversial (see “Prior breast surgery

other than excisional biopsy”)

After preoperative systemic

therapy

Controversial (see “Neoadjuvant

chemotherapy”)

Before preoperative

systemic therapy

Established

Controversial indications are those for which SLN biopsy is not univer-

sally accepted or for which the evidence behind the practice is limited or

entirely missing (see “Issues requiring further clarification”)

DCIS ductal carcinoma in situ

Eur J Nucl Med Mol Imaging

Precautions

Pregnant patients

Pregnancy is not a contraindication for radiotracer-based SLN

biopsy [18,38,39]. Blue dye should only be included in SLN

biopsy in a pregnant woman if there is clear medical need. The

use of SLN mapping involving the limited doses of radio-

tracers outlined in this guideline has been demonstrated to

expose a fetus to a negligible dose, particularly when activities

below 10 MBq are used [40]. In the case of pregnancy or

lactation, LS and SLN biopsy are justified by the low risks of

the procedure relative to the risks of axillary dissection [41].

Nonetheless, admission of a pregnant woman to a nuclear

medicine department and potential psychological concerns

must be considered before allowing the procedure.

Nursing mothers

Nursing mothers should suspend breast feeding for 24 h after

radiopharmaceutical administration.

Qualifications and responsibilities of personnel

SLN studies should only be performed by surgeons and

nuclear medicine specialists who have undergone specific

training in such procedures [41]. At this time, no defini-

tion of required training has been validated for either

surgeons or nuclear medicine specialists, although a re-

quirement of at least 30 procedures under guidance has

been proposed for each surgeon intending to perform SLN

biopsies [42–44].

Procedures in nuclear medicine

The procedure for SLN detection and localization may include

a combination of radiopharmaceutical, coloured or fluorescent

dye, preoperative scintigraphic imaging, and intraoperative

gamma probe localization followed by surgical removal of

detected SLNs.

Although there is consensus on some broad aspects of

SLN protocols in breast cancer, consensus does not exist

on all details. Controversies exist with regard to the par-

ticle size of the radiotracer, the optimal route for injection,

timing of scintigraphy and intraoperative detection, and

whether or not extra-axillary lymph nodes should be con-

sidered. The specific radiotracer and technique used are

additionally guided by local availabilities, regulations, and

practices.

False-negative rates and axillary recurrence rates have

proved to be similar regardless of the site of injection [45]. If

the goal is axillary staging only, a superficial tracer injec-

tion (periareolar, subareolar, subdermal, intradermal) may

be preferable to a deep injection (peritumoral, intratumoral)

due to better visualization of axillary SLNs [44]. Some

centres prefer dual injections, superficial and deep. The

use of dual injections captures the advantages of both

techniques and is associated with lower false-negative re-

sults [46]. If one’s aim is to stage extra-axillary nodal

basins as well as the axilla, tumour-related deep injection

is recommended [37].

Preoperative radiotracer lymphoscintigraphic mapping

is highly recommended because of the potential added

benefits in both improving accuracy and reducing mor-

bidity relative to the use of the hand-held gamma probe

alone [8]. Preoperative imaging also serves as quality

control on the use of the appropriate tracer, failure of

the injection, failure of the radiopharmaceutical, and

management of the appropriate breast and axilla—injec-

tion of the proper side (L/R). Some surgeons do not use

preoperative LS because in their environments doing so

results in scheduling delays; others do not do so be-

cause there is no evidence that LS is associated with a

higher intraoperative success rate in the harvesting of axillary

SLNs [47,48].

Patient preparation

No special preparation is required of a patient prior to her or

his arrival in the nuclear medicine department. In all patients,

recent (not older than 1 month) mammograms should be

available, as should all recent breast ultrasound images and

magnetic resonance images. All available images should be

reviewed by the nuclear medicine physician. In female pa-

tients, pregnancy status and lactating status should be deter-

mined so that appropriate steps are taken to keep the exposure

to radiation of patients, fetuses, and infants (through milk) as

low as reasonably possible.

In the nuclear medicine department, in preparation for

imaging, the patient should remove all clothing and jewellery

above the waist.

In all patients, a physical examination of the breast should

be performed by the nuclear medicine physician before injec-

tion of the radiopharmaceutical. If localization wires are in

place or if a patient has recently undergone an excisional

biopsy, such should be known by the nuclear medicine

practitioners.

It is strongly recommended that the nuclear medicine

physician communicate with the surgeon prior to and

after the imaging procedures and that such communica-

tions be documented. The communication should take

place particularly if the final report is not available prior

to surgery. The surgeon should, at the time of surgery,

have access to all images.

Eur J Nucl Med Mol Imaging

Radiopharmaceuticals

Several

99m

Tc-based agents have been used for radioguided

SLN biopsy in breast cancer. Table 2provides a summary of

those most widely investigated, including colloid particles

(antimony trisulphide—Australia and Canada; nanocolloid

albumin—Europe; sulphur colloid—USA) [49] and a novel

receptor-targeting small molecule.

The ideal radiotracer should show rapid transit to SLNs

with prolonged retention in the nodes. In general, the drain-

age, distribution, and clearance of radioactive colloids by the

lymphatic system may vary and are dependent on the size of

the particles. Small particles are drained and cleared first; large

particles are drained and cleared last and may be retained

longer at the injection site. There is general agreement that a

radiocolloid should be a good compromise between fast lym-

phatic drainage and optimal retention in SLNs [30,50]. Ide-

ally, the draining lymphatic collectors (channels) are visual-

ized so that the SLN receiving tracer from a collector can be

identified and distinguished from any second tier node that

may appear later.

The particle size also determines the timing of preoper-

ative scintigraphy and intraoperative detection of SLNs.

While smaller particles allow quick visualization of SLNs,

larger particles have slow transit in the lymphatic system

that tends to minimize visualization of non-sentinel second

tier nodes (lymph nodes downstream of SLNs) [17]. SLNs

are generally visualized within 1–2 h, and the patient

should be in the operating theatre within 2–30 h of the

injection of the colloid, depending on the facility’sschedule

[2,15,17]. If surgery is scheduled for early morning,

injection and imaging may be safely performed the after-

noon prior to the surgery [51].

Studies have shown the success rate of identification of

axillary SLNs is not significantly affected by the particle size

of the radiotracer [52–55]. Thus, the selection of radiotracer is

based more on local availability than on differences in SLN

detection. In the US,

99m

Tc-sulphur colloid is the radiocolloid

commonly used for SLN biopsy. Unfiltered

99m

Tc-sulphur

colloid comprises particles with a wide range of sizes (15–

5,000 nm, depending on the preparation method), with an

average size ranging from 305 to 340 nm. Filtered

99m

Tc-

sulphur colloid is usually obtained using a 0.22-μm filter.

The result is a suspension with colloid particles that are mostly

between 100 nm and 220 nm. A small-particle colloid,

99m

Tc-

nanocolloidal albumin (Nanocoll®), is the licensed and pre-

ferred agent in most of Europe; the size of its particles ranges

from 5 to 100 nm. The colloid used most in Australia and

Canada is

99m

Tc-antimony trisulphide; the size of the particles

most commonly used ranges from 3 to 30 nm.

The tracer must be prepared and labelled with

99m

Tc-

pertechnetate using the relevant manufacturer’s instructions.

A labelling yield greater than 90–95 % must be confirmed

before the radiopharmaceutical is injected into a patient. Hy-

persensitivity reactions to radiopharmaceuticals are rare but

have been reported. See the SNM Guideline on Radiophar-

maceuticals for general requirements [56].

An alternative to radiocolloids is the radiopharmaceutical

99m

Tc-tilmanocept (Lymphoseek®), which was approved by

the US Food and Drug Administration (FDA) in 2013.

Tilmanocept is mannosyl diethylene-triamine-pentaacetate

(DTPA) dextran. Its molecular size is approximately 7 nm.

Its uptake mechanism in lymph nodes is not dependent on

particle size as it is a macromolecule-targeting agent; it targets

dextran-mannose receptors on the surface of macrophages,

including dendritic cells in lymph nodes [50]. Dendritic cells

efficiently present the mannose receptor-mediated uptake of

Lymphoseek to T cell lymphocytes in lymph nodes [57].

Activities and volumes

Consensus on the activity to be administered in a SLN proce-

dure has not been reached. The investigated and suggested

activities vary considerably. Activities as low as 3.7 MBq

(0.1 mCi) [58] and as high as 370 MBq (10 mCi) [59]have

been used. A total injected dose of 5 to 30 MBq is generally

considered sufficient for surgery planned for the same day.

When injection is done the afternoon prior to surgery, up to

150 MBq is considered sufficient [60]. When using superficial

(periareolar, subdermal, intradermal, or subareolar) injections,

large volumes of injectate may interfere with normal lymphat-

ic flow; therefore, volumes of 0.05–0.5 mL are preferred [17].

With peritumoral injections, larger volumes (e.g. 0.5–1.0 mL)

are used [18]. When injecting small volumes (e.g. 0.1 mL), the

syringe may contain a small amount (0.1 mL) of air to clear

any dead space within the tip of the syringe and the needle.

Tabl e 2 Characteristics of

99m

Tc-based radiopharmaceuticals

Agent Particle size (nm)

Maximum Mean

Sulphur colloid 350–5,000 (see text) 100–220 (filtered)

Antimony trisulphide 80 3–30

Sulphide nanocolloid

(Lymphoscint®)

80 10–50

Nanocolloidal albumin

(Nanocoll®)

100 5–80

Rhenium sulphide

nanocolloid (Nanocis®)

500 50–200

Tin colloid 800 30–250

Labelled dextran 800 10–400

Hydroxyethyl starch 1,000 100–1,000

Stannous phytate 1,200 200–400

Tilmanoc ept

(Lymphoseek®)

About 7

(equivalence)

About 7

(equivalence)

Eur J Nucl Med Mol Imaging

Radiolabelled colloid particles are suspended; thus, they

may settle by gravity if left in a motionless syringe for more

than a few minutes. A syringe with colloid should be gently

rotated immediately prior to administration of the colloid to

ensure good mixing of the radiolabelled particles [11]. Col-

loids should not be aggressively agitated.

Injection procedure

The optimal injection technique has been the subject of lively

debate. Widely used techniques include peritumoral, subder-

mal, periareolar, intradermal, and subareolar injections. All

enable axillary SLNs to be identified accurately, and satisfac-

tory SLN detection rates have been reported for all injection

approaches. Results of multiple studies have confirmed that

the method of injection does not significantly affect the iden-

tification of axillary SLNs [61–63].

One major advantage of superficial injections is that they

are easy to perform. A subdermal, periareolar, intradermal, or

subareolar injection, however, is often more painful than a

peritumoral injection. The addition of pH-balanced 1 % lido-

caine to the radiopharmaceutical often improves patient com-

fort without compromising SLN identification [64]. The use

of peritumoral injections requires careful investigation of a

patient’s prior imaging and medical records, particularly if the

tumour is nonpalpable. If available, ultrasound guidance to

assist with placement of peritumoral injections can be helpful.

If a tumour is in the upper outer quadrant, the relatively

intense activity at the injection site may make localization of

a less-intense nearby SLN difficult [65,66].

Important advantages of deep injections are improved de-

tection of extra-axillary SLNs and the possibility of using a

larger injection volume. When administering deep injections,

care should be exercised to avoid injection into the dead space

of a seroma resulting from a previous excisional biopsy or into

a breast prosthesis.

After almost 20 years of experience, it is generally accepted

that both deep and superficial injection approaches are valid

and that they are often complementary. The combination of

both injection techniques (deep and superficial) may even

improve SLN detection and decrease false-negative findings

[46]. Although the majority of superficial lymph vessels of the

breast drain to only one SLN, a recent anatomical study on

breast lymphatics showed there are alternative lymphatic

drainage pathways to primary pathways. The authors also

found that separate lymphatic networks exist in the ventral

and dorsal parts of the breast. These drain to the axilla and the

internal mammary node (IMN) chain, respectively, without

apparent connections [67]. This observation correlates with

findings of a clinical study in which drainage to the IMN chain

and other lymph node stations outside the axilla was seen for

tumours no matter in which quadrant of the breast they were

located [68].

The site of injection can be gently massaged after tracer

administration to improve drainage of the tracer. Massage can

also be employed if passage of activity from the injection site

is delayed at any time during the study [61,62].

Imaging procedure

Quality control

Quality control should be routinely performed on the imaging

system and image display used in SLN procedures [69,70].

Quality control should be routinely performed on the gamma

probe used in the nuclear medicine department and the oper-

ating theatre for SLN procedures [71]. The reader is referred to

the SNM Guideline for General Imaging for additional infor-

mation [72].

Imaging protocol

Imaging is recommended before any operation, as there is

patient variability in breast lymphatic drainage into the

axilla and extra-axillary regions. Imaging is an efficient

means of determining if there is uptake of activity in any

node, and it improves the likelihood of identifying all

relevant node beds and thus the likelihood of locating all

SLNs [73].

Imaging system A single- or dual-head gamma-camera sys-

tem with large field-of-view (FOV) detectors is generally used

to acquire planar emission and, if desired, single-photon com-

puted tomographic (SPECT) or SPECT/CT images. Low-

energy, high-resolution (LEHR) or low-energy ultra-high res-

olution (LEUHR) collimators should be used. The energy

window should be 15 % (±5 %) centred on the 140 keV

photopeak of

99m

Tc.

Patient positions Most commonly, at each acquisition time

point at least two or three images are acquired: anterior, lateral,

and 45° anterior oblique. Anterior images are acquired with

the patient lying supine on the bed of the imaging system. In

the operating room, the patient most often lies supine with her/

his arm on the side with cancer, extended perpendicular to her/

his body. It is recommended the patient extend her/his arm as

for the anterior images. Lateral images are also acquired with

the patient lying supine, with her/his arm on the side with

cancer (R/L) extended.

For acquisition of the 45° anterior oblique images, the

patient (not the camera) should be rotated from supine to

45°, the patient’s arm on the side with cancer should be

positioned above the head, and the camera should be posi-

tioned directly above the patient. Rotation of the patient places

the breast with cancer dependent toward the patient’s midline.

This reduces attenuation of uptake in axillary nodes and

Eur J Nucl Med Mol Imaging

reduces the potential for projection overlap of the uptakes at

the injection site and in axillary nodes.

For lateral views, the patient might be rotated 90° from

supine so that she/he is lying on her/his side contralateral to

the cancer. In this position, the patient’s involved breast is

dependent toward the patient’s midline, away from the

axilla to be assessed. If rotation of a patient for 45° anterior

oblique imaging is not possible, the camera can be posi-

tioned to acquire the images. In this case, if possible, the

breast should be held toward the midline to allow better

imaging of the axilla to be assessed. If any of the above

imaging is not possible, useful images with the patient in

an upright position or in a prone position with breasts

dependent may be possible.

Image acquisition

Dynamic (flow) imaging

Although not often used in SLN procedures for breast

cancer, dynamic (flow) imaging can provide information

useful for SLN localization. If dynamic imaging is to be

performed, it should be started immediately after com-

pletion of all injections.

Planar (static) imaging

Planar (static) imaging should be performed 15–

30 min, 1 h, and 2–4 h after injection, and as needed

thereafter up to 18–24 h. At least two, preferably all three,

of the following images should be acquired: anterior, 45°

anterior oblique, and lateral. Each image acquisition is

typically 3 to 5 min in duration. For a system with large

FOV detectors, it is recommended that the pixel size be

approximately 2 mm and the matrix size be 256×256

with zoom 1 or, rarely, 128 × 128 with zoom 2. If a 2-mm

pixel size is not feasible on a system, the smallest pixel

size available should be used.

Transmission imaging

The patient’s body contour should be delineated for

positioning and referencing foci of activity. To accom-

plish this, a

Co or

99m

Tc flood source can be appropri-

ately positioned on the side of the body opposite the

camera or a

Co or

99m

Tc “point”source can be used

to trace the body contour.

Because the amount of tracer uptake in a node does not

correlate with the likelihood of it being the SLN, quanti-

fication of tracer uptake in nodes is not necessary or

helpful. In addition, removal of all axillary nodes with

radioactivity leads to fewer false-negative SLN biopsies

[74]. Anatomical localization of tracer uptake is therefore

sufficient.

Optional/alternate imaging (SPECT or SPECT/CT)

Conventional planar imaging does not give exact pre-

operative anatomical localizations of detected nodes [75].

SPECT/CT provides tomographic lymphoscintigrams

registered with anatomical data. For SPECT/CT acquisi-

tion, a patient is positioned only once—an advantage for

patients who are difficult to position. SPECT/CT pro-

vides three-dimensional images that generally have better

contrast and spatial resolution than planar images.

SPECT/CT allows the possibility of correction for effects

of attenuation and scatter. It provides relatively precise

localization of SLNs within an anatomical landscape,

thus providing a valuable road-map for surgery [76].

Based on published reports, current indications for

SPECT/CT include nonvisualization of SLN on conven-

tional planar imaging, patient obesity, and the presence of

extra-axillary SLNs, or otherwise unusual difficult-to-

characterize drainage (e.g. multiple sites of drainage,

visualization of IMN chain, intramammary lymph node,

nodes in the contralateral axilla, or previous breast sur-

gery). SPECT/CT might also be performed if the con-

ventional images are difficult to interpret (e.g. suspicion

of contamination or a SLN near the injection area)

[75–78].

SPECT acquisition for SLN detection should be

performed with a dual-detector SPECT system equipped

with LEHR or LEUHR collimators. Acquisition parame-

ters should include a matrix size of 128× 128 (4–5mm

pixels) and 120 or 128 projections over 360° with 20–

25 s/projection. If SPECT reconstruction includes reso-

lution recovery, the number of projections or the time per

projection may be reduced as recommended by the ven-

dor of the resolution recovery software.

Both low-dose CT (140 kVp, 2.5 mA) and conven-

tional CT (140 kVp, 30–150 mA) can provide useful

anatomical detail that can be used for anatomical locali-

zation and if desired, attenuation correction.

Image storage

All images obtained should be stored in a permanent

form according to national and other relevant regulations.

Skin marking

Surface marks that provide a means to triangulate SLNs

and a means to estimate their depths are desired by some

surgeons. Imaging from at least two projections should be

performed. Surface locations should be marked on the skin

with a small spot of indelible ink, and the depth of the

node should be noted. When marking the skin in the

imaging process, an attempt should be made to position

the patient as she/he would be positioned for surgery. If

more than one node is found in the same region, some

practitioners prefer to mark just the hottest node(s) and

describe and display the other nodes on accompanying

reports and images. If SPECT/CT imaging is available,

appropriate coregistered images should be made available

at the time of surgery.

Eur J Nucl Med Mol Imaging

Image processing

No particular processing procedures are needed for planar

images. Truncation of high activities (the injection sites) will

improve visualization of the SLN. A logarithmic scale to

enhance low-count areas instead of a linear scale is preferable

for image display. Processing parameters should be carefully

chosen so as to optimize image quality (see SNM Guideline

for General Imaging [72]).

Interpretation

Early and delayed lymphoscintigraphic planar images

identify SLNs in the majority of patients. Major criteria

to identify lymph nodes as SLNs are the time of ap-

pearance and occasionally visualization of lymphatic

channels (if dynamic imaging was performed). Usually,

SLNs cannot be readily distinguished from second tier

lymph nodes. The SLN is not necessarily the hottest

node, although that is often the case. Separate lymphatic

channels that drain to different lymph nodes identify

each of these as distinct SLNs, even though they may

be located in the same anatomical region. When drain-

age to more than one anatomical region is seen, each of

these regions has at least one SLN.

The report to the referring physician should describe the

orientations of the images acquired, the radiopharmaceutical,

the method of administration, the dose and volume of activity

injected, the location of the SLNs on each image, and any

source of error or inaccuracy of the procedure. The images and

report should be available by the time the patient arrives in the

surgical suite—in electronic form or as hard copy. If this is not

possible, the critical information should be relayed directly to

the surgeon. A close working relationship between the imaging

department and the surgeon are critical for accurate dissemina-

tion of information regarding numbers and locations of nodes.

Procedures in the surgical suite

Blue-dye node localization

Most breast cancer surgeons combine LS/probe information

with information obtained using blue dye injected during

surgery. This combining ofinformation is anexcellent method

for decreasing false-negative findings and increasing sensitiv-

ity [45,62].

Currently, the commonly used dyes are patent blue V,

isosulfan blue, and methylene blue. Blue dye can be injected

around the primary tumour in a manner similar to that for

radiopharmaceutical injections, 10–20 min prior to surgery in

a volume of 2–5 mL. Care should be exercised to avoid

injection into the dead space of a seroma [34]. The injection

should be performed after the patient is anaesthetized to avoid

painful injection. If local anaesthesia is to be used, the local

anaesthetic should be administered using a separate syringe

(e.g. lidocaine) since the admixture of isosulfan blue with

local anaesthetics in the same syringe results in immediate

precipitation of 4–9 % drug complex. Five minutes of mas-

sage of the injection site enhances movement of the dye

through the lymphatics to the SLN. Within 5–15 min the

SLNs are coloured. Washout is evident after approximately

45 min.

Multiple studies have established the validity of blue dyes

as markers for SLNs. The study results include reasonably

high detection rates (ranging from 75 % to 95 %) [79],

although they are slightly lower than those achieved when

radiopharmaceuticals are used. In most cases, the same SLNs

are detected by the two methods. A notable disadvantage of

using blue dyes is that blue dyes are not helpful if extra-

axillary nodes (IMN or supraclavicular nodes) are to be eval-

uated [80,81]. Another disadvantage in patients who are

having breast-conserving surgery is the temporary blue

tattooing of the skin or areola when the dye is injected

superficially.

It is important to be aware of contraindications for the use

of blue dyes. Blue dyes may interfere with pulse oximetry

readings, so in certain patients they should be used with

caution. Blue dye can induce anaphylactic reactions that re-

quire resuscitation in 0.5 to 1.0 % of patients. Hypersensitivity

to the product is the only contraindication. Blue dye should

not be used in pregnant women because of the risk of ana-

phylactic reaction. Blue dye should also not be used if there is

prior evidence of a patient having had an allergic reaction to

this type of agent or of a patient having severe renal impair-

ment [79–85].

Radioguided surgery

Detection probes must be able to detect SLNs from the

skin surface as well as within exposed surgical cavities.

The first task requires that the sensitivity of the detector is

sufficient to identify a weakly active SLN when attenuated

by up to 5 cm of soft tissue. Discriminating activity within

a SLN also requires that the probe be well collimated for a

small angle view. It is thus advisable that the major component

of collimation be in the form of a detachable collimator of

suitable construction. This allows it to be removed when it is

not required, rendering the probe more compact and more

sensitive. The detector should be constructed to offer a

high level of shielding against radiation hitting the side of

the probe assembly. The whole system should be designed

and constructed to be suitable for intraoperative use [2].

The detector itself should be ergonomically designed for

easy manoeuvrability and constructed so as to be suitable

for sterilization.

Eur J Nucl Med Mol Imaging

When used intraoperatively, a probe is placed in a sterile

bag so that it can be used in the sterile surgical field. A display

capable of providing clear instantaneous and cumulative

counts is a major requirement. It is helpful if the instantaneous

count-rate is fed to an audio signal that conveys count rate

information. Many commercial models are available with

discernible differences [69,86]. In the European Union, it is

a requirement that all medical equipment have CE certifica-

tion. Medical devices marketed in the USA must be approved

by the FDA. Neither body, however, enforces mandatory

compliance with the most widely recognized international

electromedical safety standard IEC 60601 [87]. Thus, infor-

mation regarding compatibility with regional requirements

should beseparately sought from the manufacturer of a device.

Using the images and skin markings as guides, the probe

(placed over the regions of highest counts) can be used to

select the optimum location for incision. The surgeon uses the

probe to guide dissection to the hot node(s) and places the

probe in the surgical bed after node excision to confirm

removal of the hot node(s). In working with the probe, it is

important to direct the probe away from activity at the injection

sites. Counts are recorded per unit time with the probe in the

operative field, over the node before excision (in vivo), and

after excision (ex vivo). A background tissue count is also

recorded with the probe pointing away from the injection site,

nodal activity, or other physiological accumulations (e.g. liver).

The identified SLNs are removed by the surgeon. When a

hot node has been removed, the wound site should be checked

for remaining activity. Due to the limited spatial resolution of

gamma cameras, nodes closer than about 15–20 mm may

appear as one spot. Thus, after removal of one node, another

hot node may still be present. The current use of SPECT/CT

may reveal the presence of a cluster of lymph nodes on CT

images. The number of nodes to remove from any one basin

will depend on the report from LS and local practice [88,89].

Deeply located SLNs are difficult to detect because of

attenuation and radioactivity at the injection site that may

cause nearby SLNs to be hidden. This situation is observed

mostly when tumours are in the superior outer quadrant and

when tumours are located in inner quadrants and SLNs are in

the IMN. It is advisable to use smaller diameter probes (e.g.

10 mm diameter probes) in intercostal areas as they generally

allow focal activity in limited surgical spaces to be localized

more easily [90]. The use of SPECT/CT images can help

localize focal activity as can the use of intraoperative imaging

with portable gamma cameras [91,92].

Patients who have undergone previous breast surgery or

received radiation may demonstrate nodes in locations not

typically seen in patients without a history of prior surgery.

The lymphatic duct to the original SLN may be obstructed by

tumour growth or the original SLN may be entirely replaced

by disease. Consequently, lymphatic drainage may be either

diverted to a non-sentinel node or no lymph nodes may be

visualized, increasing false-negative results. To minimize

false-negative results, the open axilla should be palpated and

suspicious lymph nodes harvested, even if these are neither

hot nor blue. In cases of nonvisualization or if the SLN is

located outside the lower medial part of the axilla, palpation of

the typical SLN area is particularly important [93].

Radioactive waste in the operating room (sponges,

etc.) and in pathology should be collected according to

institutional radiation safety procedures. This waste will

also be a biohazard and should be handled accordingly.

Personnel not accustomed to dealing with radioactive

materials should be educated as to their safe handling

and disposal. Appropriate education of surgical suite

personnel and pathologists will often be very valuable for

the establishment of appropriate handling of radioactive ma-

terials, reassurance of concerned individuals and expedient

processing of tissues.

SLN nonvisualization

The majority of patients with preoperative lymphoscintigraphic

SLN nonvisualization will have at least one SLN detected

intraoperatively, either by gamma probe alone or by gamma

probe combined with blue dye. While logistically difficult in

most centres, a second radiotracer injection, at perhaps a dif-

ferent injection site, may be useful to visualize previously

nonvisualized SLNs.

In approximately 1 to 2 % of patients, SLNs will not be

detected preoperatively or intraoperatively and the status of

the axillary nodes cannot be determined. Old age, obesity,

tumour location other than the upper outer quadrant, and

nonvisualization of SLNs on preoperative LS may be associ-

ated with failed SLN localization [94]. The significance of

preoperative scintigraphic nonvisualization is not yet known.

Some studies have suggested that patients with unsuccessful

axillary mapping may have an increased risk of positive

axillary involvement [95]. There is no definitive consensus

on what to do if a SLN cannot be visualized. However, current

standards of care recommend ALND when intraoperative

SLN identification is not achieved [96].

Multiple SLNs

In principle, SLN biopsy requires the removal of all SLNs

receiving direct lymphatic drainage from the site of the

primary tumour. In practice, this is not always achieved.

The question remains as to how many SLNs should be

biopsied when multiple nodes are found. In patients with

multiple radiolabelled nodes, it is often difficult to distin-

guish between SLNs and second tier nodes. However,

removing more than five nodes from the axilla does not

result in marked improvement in the sensitivity of axillary

SLN biopsy [90–100].

Eur J Nucl Med Mol Imaging

Histopathology

Before specimens are sent for histological examination, they

should be evaluated ex vivo using the probe to demonstrate

that they are radioactive [101]. This evaluation should be

performed on all nodal specimens and all tumour specimens.

Histopathological assessment of SLNs is the “gold stan-

dard”procedure for the subsequent surgical management of

breast cancer patients. However, this gold standard is highly

variable among centres. In many institutions, SLNs are

assessed intraoperatively using imprint cytology, frozen sec-

tioning, or both, and more thoroughly after the operation. The

sensitivity of the intraoperative diagnosis is variable and many

facilities do not adopt it at all [102]. Some molecular methods

have been used previously for SLN diagnosis, but have shown

a lack of reproducibility, require a longer time for the

intraoperative assessment, and provide no means to study

the whole lymph node. A new molecular method has been

developed recently. It is based on a one-step nucleic acid

amplification (OSNA) method. This procedure is in validation

studies in many centres; it is in routine use in others [103].

Radiation dosimetry

Nuclear medicine, surgery, and pathology professionals are

involved if a radiopharmaceutical is used in a SLN procedure.

Each involved practitioner and the patients receiving such

procedures are exposed to radiation. The exposures received

by each, when doses standard for SLN procedures are admin-

istered, are well below recommended limits for both public

and thus occupational exposures.

Estimates of exposures to patients [101,104–110], sur-

geons [101,105,107,111–117], and pathologists [101,105,

112–115,118,119] have been reported by several investiga-

tors and are offered in relevant radiopharmaceutical package

inserts [120,121]. Table 3is a summary and interpretation of

much of the available data.

All of the published data indicate that exposures to patients

and professionals from SLN procedures are minimal. Low

patient effective dose and very low fetus/uterus equivalent

dose [39,40,101,109,110,123] indicate exposure to radiation

is not a contraindication for a SLN procedure in any patient,

including pregnant patients. However, prudence dictates that

care should be exhibited when conducting a SLN procedure on

any patient. In patients who are breast feeding, nursing should

be suspended for 24 h following radiopharmaceutical admin-

istration. Regarding professionals, the United States Nuclear

Regulatory Commission (NRC) has determined that the expo-

sures to pathologists from radioactive SLN specimens are too

small to require regulation [124]. The injection site absorbed

dose can be significant (see able 3). There are no known

negative consequences of this. The site is often, but not always,

excised. The dose is very small relative to that received from

postoperative radiation therapy. Because exposures in SLN

procedures of all non-nuclear medicine personnel are low,

none need be monitored routinely for radiation exposure. The

decision to badge personnel involved only with SLN proce-

dures is at the discretion of individuals and local custom.

Absorbed doses and equivalent doses to several organs

have been estimated and can be found in tables in a few

publications and relevant package inserts [104,106,110,

120,121,125]. The dose to a patient from a transmission

source will vary. One estimate of the dose from a transmission

source is 0.003 mSv [106,107]. The dose from a CT scan also

varies. One estimate of the dose from the CT element of a

SPECT/CT scan is 2.4 mSv [126]. A low-dose CT scan with a

field of view limited to avoid radiosensitive tissues can help

Tabl e 3 Ranges of estimates of radiation exposures

Radiation exposure Range of estimates

× 18.5 MBq × 100 patients/year

Public limit

Occupational limit

Injection site absorbed dose 1 to 50 mGy/MBq <925 mGy

Injected breast equivalent dose 0.03 to 0.8 (mSv/MBq) <15 mSv

Patient effective dose

0.002 to 0.03 (mSv/MBq) <0.56 mSv <1 mSv

Fetus/uterus equivalent dose 0.00003 to 0.0009 (mSv/MBq) <0.017 mSv <1 mSv

Surgeon lens-of-eye equivalent dose 0.00009 (mSv/MBq) <0.17 (mSv/year) <15 (mSv/year) <150 (mSv/year)

Surgeon hand equivalent dose 0.0004 to 0.01 (mSv/MBq) <19 (mSv/year) <50 (mSv/year) <500 (mSv/year)

Surgeon effective dose 0.00004 to 0.0003 (mSv/MBq) <0.56 (mSv/year) <1 (mSv/year) <20 (mSv/year)

Pathologist lens-of-eye equivalent dose 0.00001 to 0.00003 (mSv/MBq) <0.056 (mSv/year) <15 (mSv/year) <150 (mSv/year)

Pathologist hand equivalent dose 0.00001 to 0.001 (mSv/MBq) <1.9 (mSv/year) <50 (mSv/year) <500 (mSv/year)

Pathologist effective dose 0.000004 to 0.0002 (mSv/MBq) <0.37 (mSv/year) <1 (mSv/year) <20 (mSv/year)

Estimates extracted or derived from information in the included references

Assuming that SLN procedures were conducted on 100 patients in a year and assuming each patient was injected with a dose of 18.5 MBq (0.5 mCi)

International Commission on Radiological Protection (ICRP) recommended limits [122]

Pregnant-woman effective-dose estimate and limit are the same as those for a non-pregnant patient

Eur J Nucl Med Mol Imaging

keep the equivalent dose to a minimum. The estimates are

dependent on various acquisition parameters. The total expo-

sure in such cases is the emission-generated dose plus the

transmission-generated dose.

Issues requiring further clarification

T3 and T4 tumours

Evidence regarding the efficacy of SLN biopsy is mainly

based on studies including only T1 and small T2 tumours. A

few reports suggest that false-negative rates in the case of

large tumours are similar to those for small tumours; however,

more evidence is needed for definitive confirmation of this

[127,128].

Multifocal and multicentric tumours

Multifocal breast cancer is defined as two or more separate

foci of ductal carcinoma that are more than 2 cm apart within

the same quadrant; multicentric breast cancer is the presence

of separate independent foci of carcinoma in different quad-

rants [129]. Both types of cancer have high prevalence of

axillary metastases, and both have high reported false-

negative rates [130]. Despite those factors, which raise con-

cerns, acceptable axillary recurrence rates have been reported

[127–131].

Ductal carcinoma in situ

Ductal carcinoma in situ (DCIS) does not metastasize to

regional lymph nodes, but ductal invasion is missed in up to

40 % of patients with DCIS. Because this is the case, SLN

biopsy is recommended in patients with DCIS undergoing

mastectomy [132]. In patients in whom breast conservation

is planned, if invasion is detected in a surgical specimen, SLN

biopsy can be performed later. However, wide local excision

can alter lymphatic drainage, especially to IMNs. Because

local invasion can be missed on initial diagnostic biopsy, some

centres choose to perform SLN biopsy in all patients with

DCIS to avoid a less-accurate SLN biopsy after wide local

excision [133].

Suspicious palpable nodes

Palpable axillary nodes may be tumour-negative in up to 40 %

of patients [134]. One widely accepted practice for assessment

of suspicious palpable nodes is preoperative axillary ultrasound

scan with fine needle aspiration cytology or core needle biopsy.

Another accepted practice is to perform SLN biopsy if palpable

nodes are negative following preoperative evaluation. In this

case, suspicious palpable nodes should be harvested for histo-

pathological evaluation, even when neither hot nor blue.

Evaluation of internal mammary and other extra-axillary

nodes

Internal mammary SLN detection rates are significantly

affected by depth of radiopharmaceutical injection. It is

generally recognized that mapping of IMNs requires deep

injection of radiopharmaceuticals, either peritumoral or

intratumoral [135–137]. In some studies, IMNs have been

detected in about one-third of patients with breast cancer,

of which about 63–92 % could be harvested during sur-

gery. Of the harvested IMNs, 11–27 % had metastases

[138–140]. There is no doubt that metastasis in the IMNs

significantly worsens prognosis in breast cancer, and pre-

dictive models suggest that it is under-treatment of such

metastases that is the cause of the poorer prognosis in

medial quadrant tumours versus lateral quadrant tumours

[141]. However, the significance of IMN biopsy con-

tinues to be discussed. There is evidence that mapping

of IMNs leads to stage migration and to modifications

of treatment planning with respect to radiotherapy and

systemic therapy, but more evidence is necessary to

support the idea that mapping of IMNs will improve

the outcome of treatment and survival [140,142]. If complete

SLN biopsy in breast cancer is the aim, peritumoral injection

of tracer is required.

Prior excisional biopsy

Lymph drainage is probably changed in patients who have

undergone breast surgery. Non-axillary drainage has been

identified more often in re-operative SLN biopsy than in

primary SLN biopsy [133]. However, there is evidence that

successful SLN biopsy can be performed in proximity to the

site of a previous breast biopsy [143,144].

Prior breast surgery other than excisional biopsy

SLN biopsy can be performed following local recurrence after

breast conservation in DCIS patients. Furthermore, plastic

surgery with breast augmentation or reduction does not con-

traindicate the SLN procedure [145].

Prioraxillarysurgery

A second SLN biopsy can be performed following local

recurrence after breast conservation and negative axillary

SLN biopsy. The success rate may be lower than with a

primary SLN biopsy. Furthermore, extra-axillary SLNs are

visualized more frequently in patients with prior axillary sur-

gery. Encouraging results have been reported regarding detec-

tion of axillary recurrences, but the evidence is not conclusive

[146]. On the other hand, there is no evidence that these

patients benefit from diagnostic ALND.

Eur J Nucl Med Mol Imaging

Neoadjuvant chemotherapy

SLN biopsy gives precise axillary staging prior to neoadjuvant

chemotherapy; however, prechemotherapy SLN biopsy may

delay the start of treatment, and require an additional surgery.

After neoadjuvant chemotherapy, SLN biopsy may lead to an

underestimation of the initial stage [34,147]. On the other

hand, axillary nodal status after neoadjuvant therapy is a

highly significant prognostic factor. Pathological complete

response in the axilla can be achieved in up to 40 % of

patients. ALND and associated morbidity are avoided in these

patients. Available data show that there are, in this category of

patients, no significant differences in the success rate of SLN

biopsy when compared with patients not having neoadjuvant

chemotherapy [148–150].

Acknowledgments The authors acknowledge the members of the

EANM Oncology Committee, of the European Society of Surgical On-

cology (ESSO), of the EANM Executive Committee, and of the SNMMI

Committee on Guidelines for their contributions to the preparation of this

guideline.

The Oncology Committee of EANM consists of the following

individuals:

Francesco Giammarile, MD, PhD (chair) (Université Claude Bernard,

Hospices Civils, Lyon, France), Sally Barrington, MD (St. Thomas'

Hospital, London, UK), Ambros Beer, MD (Klinikum rechts der Isar,

Technische Universität, Munich, Germany), Fani Bozkurt, MD, PhD

(Hacettepe University Medical School, Ankara, Turkey), Roberto

Delgado-Bolton, MD (Hospital Clínico San Carlos, Madrid, Spain),

Stefano Fanti, MD, PhD (University of Bologna, Italy), Ken Hermann,

MD (Technische Universität, Munich, Germany), Jolanta Kunikowska,

MD (Medical University, Warsaw, Poland), Werner Langsteger, MD,

PhD (St Vincent's Hospital, Linz, Austria), Michel Meignan, MD, PhD

(Hopital Henri Mondor, Créteil, France), Felix Mottaghy, MD, PhD

(Universitätsklinikum Aachen, Germany), Wolfgang Weber, MD, PhD

(University of Freiburg, Germany)

The Committee on SNMMI Guidelines consists of the following

individuals:

Kevin J. Donohoe, MD (Chair) (Beth Israel Deaconess Medical Cen-

ter, Boston, MA); Sue Abreu, MD (Sue Abreu Consulting, Nichols Hills,

OK);Helena Balon, MD (Beaumont Health System, Royal Oak, MI);

Twyla Bartel, DO (UAMS, Little Rock, AR); Paul E. Christian, CNMT,

BS, PET (Huntsman Cancer Institute, University of Utah, Salt Lake City,

UT); Dominique Delbeke, MD (Vanderbilt University Medical Center,

Nashville, TN); Vasken Dilsizian, MD (University of Maryland Medical

Center, Baltimore, MD); Kent Friedman, MD (NYU School ofMedicine,

New York, NY); James R. Galt, PhD (Emory University Hospital, Atlan-

ta, GA); Jay A. Harolds, MD (OUHSC-Department of Radiological

Science, Edmond, OK); Aaron Jessop, MD (UT MD Anderson Cancer

Center, Houston, TX); David H. Lewis, MD (Harborview Medical Cen-

ter, Seattle, WA); J. Anthony Parker, MD, PhD (Beth Israel Deaconess

Medical Center, Boston, MA); James A. Ponto, RPh, BCNP (University

of Iowa, Iowa City, IA); Lynne T. Roy, CNMT (Cedars/Sinai Medical

Center, Los Angeles, CA); Schoder, MD (Memorial Sloan-Kettering

Cancer Center, New York, NY); Barry L. Shulkin, MD, MBA (St. Jude

Children’s Research Hospital, Memphis, TN); Michael G. Stabin, PhD

(Vanderbilt University, Nashville, TN); Mark Tulchinsky, MD (Milton S.

Hershey Med Center, Hershey, PA)

The EANM Executive Committee consists of the following individuals:

Fred Verzijlbergen, MD, PhD (Erasmus MC Centreal Location, Rot-

terdam, Netherlands); Arturo Chiti, MD (Istituto Clinico Humanitas,

Rozzano Mi, Italy); Savvas Frangos, MD (Bank of Cyprus Oncology

Center, Strovolos, Nicosia Cyprus); Jure Fettich, MD (University Medi-

cal Centre Ljubljana, Ljubljana, Slovenia); Bernd J. Krause, MD, PhD

(Universitätsklinikum Rostock, Rostock, Germany); Dominique Le

Guludec, PhD (Hopital Bichat, Paris, France); Wim Oyen, MD, PhD

(Radboud University Medical Centre, Numegen, Netherlands)

References

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA

Cancer J Clin. 2010;60:277–300.

2. Keshtgar MRS, Ell PJ. Sentinel lymph node detection and imaging.

Eur J Nucl Med. 1999;26:57–67.

3. Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA,

Storm FK, et al. Technical details of intraoperative lymphatic

mapping for early stage melanoma. Arch Surg. 1992;127:

392–9.

4. Krag DN, Weaver D, Alex JC, Fairbank JT. Surgical resection and

radiolocalization of sentinel lymph node in breast cancer using a

gamma probe. Surg Oncol. 1993;2:335–9.

5. Giuliano AE, Kirgan D, Guenther JM. Lymphatic mapping and

sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:

391–401.

6. Noguchi M, Katev N, Miyazaki I. Diagnosis of axillary lymph node

metastases in patients with breast cancer. Breast Cancer Res Treat.

1996;40:283–93.

7. Taylor A, Murray D, Herda S, Vansant J, Alazraki N. Dynamic

lymphoscintigraphy to identify the sentinel and satellite nodes. Clin

Nucl Med. 1996;21:755–8.

8. PijpersR, Meijer S, Hoekstra OS, Collet GJ, Comans EF, Boom RP,

et al. Impact of lymphoscintigraphy on sentinel node identification

with technetium-99m-colloid albumin in breast cancer. J Nucl Med.

1997;38:366–8.

9. Giuliano AE. Lymphatic mapping and sentinel node biopsy in

breast cancer. JAMA. 1997;277:791–2.

10. Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni

M, et al. Sentinel node biopsy to avoid axillary dissection in breast

cancer patients with clinically negative lymph-nodes. Lancet.

1997;349:1864–7.

11. International Breast Cancer Consensus Conference. Image-detected

breast cancer: state of the art diagnosis and treatment. J Am Coll

Surg. 2001;193:297–302.

12. Benson JR, Della Rovere GQ, Axilla Management Consensus

Group. Management of the axilla in women with breast cancer.

Lancet Oncol. 2007;8:331–48.

13. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V,

et al. A randomized comparison of sentinel-node biopsy with routine

axillary dissection in breast cancer. N Engl J Med. 2003;349:546–53.

14. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V,

et al. Sentinel-lymph-node biopsy as a staging procedure in breast

cancer: update of a randomized controlled study. Lancet Oncol.

2006;7:983–90.

15. Buscombe J, Paganelli G, Burak ZE, Waddington W, Maublant J,

Prats E, et al. Sentinel node in breast cancer procedural guidelines.

Eur J Nucl Med Mol Imaging. 2007;34:2154–9.

16. Zaknun JJ, Giammarile F, Valdes Olmos RA, Vidal-Sicart S,

Mariani G. Changing paradigms in radioguided surgery and

intraoperative imaging: the GOSTT concept. Eur J Nucl Med Mol

Imaging. 2012;39:1–3.

17. De CiccoC, Cremonesi M, Luini A, Bartolomei M, Grana C, Prisco

G, et al. Lymphoscintigraphy and radioguided biopsy of the sentinel

axillary node in breast cancer. J Nucl Med. 1998;39:2080–4.

18. Kaufmann M, Morrow M, von Minckwitz G, Harris JR, Biedenkopf

Expert Panel Members. Locoregional treatment of primary breast

Eur J Nucl Med Mol Imaging

cancer: consensus recommendations from an International Expert

Panel. Cancer. 2010;116:1184–91.

19. Straver ME, Meijnen P, van Tienhoven G, van de Velde CJ, Mansel

RE, Bogaerts J, et al. Role of axillary clearance after a tumor-

positive sentinel node in the administration of adjuvant therapy in

early breast cancer. J Clin Oncol. 2010;28(5):731–7.

20. van la Parra RF, Peer PG, Ernst MF, Bosscha K. Meta-analysis of

predictive factors for non-sentinel lymph node metastases in breast

cancer patients with a positive SLN. Eur J Surg Oncol. 2011;37:

290–9.

21. Unal B, Gur AS, Kayiran O, Johnson R, Ahrendt G, Bonaventura

M, et al. Models for predicting non-sentinel lymph node positivity

in sentinel node positive breast cancer: the importance of scoring

system. Int J Clin Pract. 2008;62:1785–91.

22. Sanjuán A, Escaramís G, Vidal-Sicart S, Illa M, Zanón G, Pahisa J,

et al. Predicting non-sentinel lymph node status in breast cancer

patients with sentinel lymph node involvement: evaluation of two

scoring systems. Breast J. 2010;16:134–40.

23. Cserni G, Boross G, Maráz R, Leidenius MH, Meretoja TJ, Heikkila

PS, et al. Multicenter validation of different predictive tools of non-

sentinel lymph node involvement in breast cancer. Surg Oncol.

2012;21:59–65.

24. Giuliano AE, McCall L, Beitsch P, Whitworth PW,

Blumencranz P, Leitch AM, et al. Locoregional recurrence after

sentinel lymph node dissection with or without axillary dissec-

tion in patients with sentinel lymph node metastases: the

American College of Surgeons Oncology Group Z0011 ran-

domized trial. Ann Surg. 2010;252:426–32.

25. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW,

Blumencranz PW, et al. Axillary dissection vs no axillary dissection

in women with invasive breast cancer and sentinel node metastasis:

a randomized clinical trial. JAMA. 2011;305:569–75.

26. de Boer M, van Deurzen CH, van Dijck JA, Borm GF, van

Diest PJ, Adang EM, et al. Micrometastases or isolated tumor

cells and the outcome of breast cancer. N Engl J Med. 2009;361:

653–63.

27. Degnim AC, Zakaria S, Boughey JC, Sookhan N, Reynolds C,

Donohue JH, et al. Axillary recurrence in breast cancer patients

with isolated tumor cells in the sentinel lymph node [AJCC N0(i+)].

Ann Surg Oncol. 2010;17:2685–9.

28. Giuliano AE, Hawes D, Ballman KV, Whitworth PW, Blumencranz

PW, Reintgen DS, et al. Association of occult metastases in sentinel

lymph nodes and bone marrow with survival among women with

early-stage invasive breast cancer. JAMA. 2011;306:385–93.

29. Giobuin SM, Kavanagh DO, Myers E, Doherty AO, Quinn CM,

Crotty T, et al. The significance of immunohistochemistry positivity

in sentinel nodes which are negative on haematoxylin and eosin in

breast cancer. Eur J Surg Oncol. 2009;35:1257–60.

30. Lyman GH, Giuliano AE, Somerfield MR, Benson 3rd AB,

Bodurka DC, Burstein HJ, et al. American Society of Clinical

Oncology guideline recommendations for sentinel lymph node

biopsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703–20.

31. Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B,

Senn HJ, et al. Thresholds for therapies: highlights of the St Gallen

International Expert Consensus on the primary therapy of early

breast cancer 2009. Ann Oncol. 2009;20:1319–29.

32. Edge SB, Compton CC. The American Joint Committee on Cancer:

the 7th edition of the AJCC cancer staging manual and the future of

TNM. Ann Surg Oncol. 2010;17:1471–4.

33. Galimberti V, Zurrida S, Zucali P, Luini A. Can sentinel node biopsy

avoid axillary dissection in clinically node-negative breast cancer

patients? Breast. 1998;7:8–10.

34. Schwartz GF, Giuliano AE, Veronesi U, Consensus Conference

Committee. Proceedings of the Consensus Conference on the role

of sentinel lymph node biopsy in carcinoma of the breast. Breast.

2002;11:362–73.

35. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP,

Ashikaga T, et al. Technical outcomes of sentinel-lymph-node

resection and conventional axillary-lymph-node dissection in pa-

tients with clinically node-negative breast cancer: results from the

NSABP B-32 randomised phase III trial. Lancet Oncol. 2007;8:

881–8.

36. Purushotham AD, Upponi S, Klevesath MB, Bobrow L, Millar K,

Myles JP, et al. Morbidity after sentinel lymph node biopsy in

primary breast cancer: results from a randomized controlled trial. J

Clin Oncol. 2005;23:4312–21.

37. van der Ploeg IM, Nieweg OE, van Rijk MC, Valdes Olmos

RA, Kroon BB. Axillary recurrence after a tumor-negative

sentinel node biopsy in breast cancer patients: a systematic

review and meta-analysis of the literature. Eur J Surg Oncol.

2008;34:1277–84.

38. Amersi F, Hansen NM. The benefits and limitations of sentinel

lymph node biopsy. Curr Treat Options Oncol. 2006;7:141–51.

39. Keleher A, Wendt 3rd R, Delpassand E, Stachowiak AM, Kuerer

HM. The safety of lymphatic mapping in pregnant breast cancer

patients using Tc-99m sulfur colloid. Breast J. 2004;10:492–5.

40. Gentilini O, Cremonesi M, Trifirò G, Ferrari M, Baio SM,

Caracciolo M, et al. Safety of sentinel node biopsy in pregnant

patients with breast cancer. Ann Oncol. 2004;15:1348–51.

41. Morita ET, Chang J, Leong SP. Principles and controversies in

lymphoscintigraphy with emphasis on breast cancer. Surg Clin

North Am. 2000;80:1721–39.

42. Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg VS, Shriver C,

et al. The sentinel node in breast cancer –a multi-center validation

study. N Engl J Med. 1998;339:941–6.

43. Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel

lymphadenectomy in breast cancer. J Clin Oncol. 1997;15:

2345–50.

44. Martin 2nd RC, Edwards MJ, Wong SL, Tuttle TM, Carlson DJ,

Brown CM, et al. Practical guidelines for optimal gamma probe

detectionof sentinel lymph nodes in breast cancer: results of a multi-

institutional study. For the University of Louisville Breast Cancer

Study Group. Surgery. 2000;128:39.

45. Pesek S, Ashikaga T, Krag LE, Krag D. The false-negative rate of

sentinel node biopsy in patients with breast cancer: a meta-analysis.

World J Surg. 2012;36:2239–51.

46. HindieE, GroheuxD, Espie M,Bourstyn E,Toubert ME, Sarandi F,

et al. Sentinel node biopsy in breast cancer. Bull Cancer. 2009;96:

713–25.

47. McMasters KM, Wong SL, Tuttle TM, Carlson DJ, Brown CM,

Noyes RD, et al. Preoperative lymphoscintigraphy for breast cancer

does not improve the ability to identify axillary sentinel lymph

nodes. Ann Surg. 2000;231:724–31.

48. Marchal F, Rauch P, Morel O, Mayer JC, Olivier P, Leroux A, et al.

Results of preoperative lymphoscintigraphy for breast cancer are

predictiveof identification of axillary sentinel lymphnodes. World J

Surg. 2006;30:55–62.

49. Wilhelm AJ, Mijnhout GS, Franssen EJF. Radiopharmaceuticals in

sentinel lymph-node detection –an overview. Eur J Nucl Med.

1999;26:S36–42.

50. Vera DR, Wallace AM, Hoh CK. A synthetic macromolecule for

sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. J Nucl

Med. 2001;42:951–9.

51. Babiera GV, Delpassand ES, Breslin TM, Ross MI, Ames FC,

Singletary SE, et al. Lymphatic drainage patterns on early

versus delayed breast lymphoscintigraphy performed after injec-

tion of filtered Tc-99m sulfur colloid in breast cancer patients

undergoing sentinel lymph node biopsy. Clin Nucl Med. 2005;

30(1):11–5.

52. Mariani G, Moresco I, Viale G, Villa G, Bagnasco M, Canavese G,

et al. Radioguided sentinel lymph node biopsy in breast cancer

surgery. J Nucl Med. 2001;42:1198–215.

Eur J Nucl Med Mol Imaging

53. Clarke D, Khoni N, Mansel ER. Sentinel node biopsy in breast

cancer. ALMANAC trial. World J Surg. 2001;25:819–22.

54. Bourgeois P. Scintigraphic investigations of the lymphatic system:

the influence of injected volume and quantity of labeled colloidal

tracer. J Nucl Med. 2007;48:693–5.

55. Burak WE, Agnese DM, Povoski SP. Advances in the surgical

management of early stage invasive breast cancer. Curr Probl

Surg. 2004;41:877–936.

56. Callahan RJ, Chilton HM, Ponto JA, Swanson DP, Royal HD,

Bruce AD. Procedure guideline for the use of radiopharmaceuticals

4.0. J Nucl Med Technol. 2007;35(4):272–5.

57. Engering AJ, Cella M, Fluitsma D, Brockhaus M, Hoefsmit EC,

Lanzavecchia A, et al. The mannose receptor functions as a high

capacity and broad specificity antigen receptor in human dendritic

cells. Eur J Immunol. 1997;27(9):2417–25.

58. McCarter MD, Yeung H, Yeh S, Fey J, Borgen PI, Cody 3rd HS.

Localization of the sentinel node in breast cancer: identical results

with same-day and day-before isotope injection. Ann Surg Oncol.

2001;8:682–6.

59. van der Ent FW, Kengen RA, van der Pol HA, Hoofwijk AG.

Sentinel node biopsy in 70 unselected patients with breast cancer:

increased feasibility by using 10 mCi radiocolloid in combination

with a blue dye tracer. Eur J Surg Oncol. 1999;25:24–9.

60. Gray RJ, Pockaj BA, Roarke MC. Injection of 99mTc-labeled sulfur

colloid the day before operation for breast cancer sentinel lymph

node mapping is as successful as injection the day of operation. Am

J Surg. 2004;188:685–9.

61. Nieweg OE, Estourgie SH, van Rijk MC, Kroon BB. Rationale for

superficial injection techniques in lymphatic mapping in breast

cancer patients. J Surg Oncol. 2004;87:153–6.

62. Noguchi M, Inokuchi M, Zen Y. Complement of peritumoral and

subareolar injection in breast cancer sentinel lymph node biopsy. J

Surg Oncol. 2009;100:100–5.

63. Linehan DC, Hill ADK, Akhurst T, Yeung H, Yeh SD, Tran KN,

et al. Intradermal radiocolloid and intraparenchymal blue dye injec-

tion optimize sentinel node identification in breast cancer patients.

Ann Surg Oncol. 1999;6(5):286–93.

64. Stojadinovic A, Peoples GE, Jurgens JS, Howard RS, Schuyler B,

Kwon KH, et al. Standard versus pH-adjusted and lidocaine

supplemented radiocolloid for patients undergoing sentinel-lymph-

node mapping and biopsy for early breast cancer (PASSION-P

trial): a double-blind, randomised controlled trial. Lancet Oncol.

2009;10(9):849–54.

65. Pelosi E, Bello M, Griors M, Ala A, Giani R, Bussone R, et al.

Sentinel lymph node detection in patients with early-stage breast

cancer: comparison of periareolar and subdermal/peritumoral injec-

tion techniques. J Nucl Med. 2004;45:220–5.

66. Chakera AH, Friis E, Hesse U, Al-Suliman N, Zerahn B, Hesse B.

Factors of importance for scintigraphic non-visualization of sentinel

nodes in breast cancer. Eur J Nucl Med Mol Imaging. 2005;32:286–

93.

67. Suami H, Pan WR, Mann GB, Taylor GI. The lymphatic anatomy of

the breast and its implications for sentinel lymph node biopsy: a

human cadaver study. Ann Surg Oncol. 2008;15:863–71.

68. Uren RF, Howman-Giles RB, Thompson JF, Malouf D, Ramsey-

Stewart G, Niesche FW, et al. Mammary lymphoscintigraphy in

patients with breast cancer –mapping lymph drainage patterns and

locating the sentinel nodes. J Nucl Med. 1995;36:1775–80.

69. NEMA. NU 1-2007 Performance measurements of scintillation

cameras. National Electrical Manufacturers Association; 2007.

http://www.nema.org/stds/nu1.cfm (accessed March 2013).

70. International Electrotechnical Commission. Nuclear medicine in-

strumentation –Routine tests –Part 2: Scintillation cameras and

single photon emission computed tomography imaging. IEC/TR

61948–2 ed1.0 Geneva: IEC; 2001. http://webstore.iec.ch/

webstore/webstore.nsf/Artnum_PK/26717 (accessed March 2013).

71. NEMA. NU 3-2004 Performance measurements and quality control

guidelines for non-imaging intraoperative gamma probes. National

Electrical Manufacturers Association; 2004. http://www.nema.org/

stds/nu3.cfm (accessed March 2013).

72. The SNM procedure guideline for general imaging 6.0. http://

interactive.snm.org/docs/General_Imaging_Version_6.0.pdf

(accessed March 2013).

73. Alazraki NP, Styblo T, Grant SF, Cohen C, Larsen T, Aarsvold JN.

Sentinel node staging of early breast cancer using lymphoscintigraphy

and the intraoperative gamma-detecting probe. Radiol Clin North

Am. 2001;39:947–56.

74. Goyal A, Newcombe RG, Chhabra A, Mansel RE, ALMANAC

Trialists Group. Factors affecting failed localisation and false-

negative rates of sentinel node biopsy in breast cancer –results of

the ALMANAC validation phase. Breast Cancer Res Treat.

2006;99(2):203–8.

75. Lerman H, Metser U, Lievshitz G, Sperber F, Shneebaum S, Even-

Sapir E. Lymphoscintigraphic sentinel node identification in pa-

tients with breast cancer: the role of SPECT-CT. Eur J Nucl Med

Mol Imaging. 2006;33:329–37.

76. Keidar Z, Israel O, Krausz Y. SPECT/CT in tumor imaging: tech-

nical aspects and clinical applications. Semin Nucl Med. 2003;33:

205–18.

77. van der Ploeg IM, Nieweg OE, Kroon BB, Rutgers EJ, Baas-

Vrancken Peeters MJ, Vogel WV, et al. The yield of SPECT/CT

for anatomical lymphatic mapping in patients with breast cancer.

Eur J Nucl Med Mol Imaging. 2009;36:903–9.

78. Vermeeren L, van der Ploeg IM, Valdes Olmos RA, Meinhardt W,

Klop WM, Kroon BB, et al. SPECT/CT for preoperative sentinel

node localization. J Surg Oncol. 2010;101:184–90.

79. Anan K, Mitsuyama S, Kuga H, Saimura M, Tanabe Y, Suehara N,

et al. Double mapping with subareolar blue dye and peritumoral

green dye injections decreases the false negative rate of dye only

sentinel node biopsy for early breast cancer: 2 site injection is more

accurate than 1-site injection. Surgery. 2006;139:624–9.

80. RodierJF, Velten M, Wilt M, Martel P, Ferron G, Vaini-Elies V, et al.

Prospective multicentric randomized study comparing periareolar

and peritumoral injection of radiotracer and blue dye for the detec-

tion of sentinel lymph node in breast sparing procedures:

FRANSENODE trial. J Clin Oncol. 2007;25:3664–9.

81. Varghese P, Abdel-Rahman AT, Akberali S, Mostafa A, Gattuso JM,

Carpenter R. Methylene blue dye –a safe and effective alternative

for sentinel lymph node localization. Breast J. 2008;14:61–7.

82. Albo D, Wayne JD, Hunt KK, Rahlfs TF, Singletary SE, Ames

FC, et al. Anaphylactic reactions to isosulfan blue dye during

sentinel lymph node biopsy for breast cancer. Am J Surg.

2001;182:393–8.

83. Montgomery LL, Thorne AC, Van Zee KJ, Fey J, Heerdt AS,

Gemignani M, et al. Isosulfan blue dye reactions during sentinel

lymph node mapping for breast cancer. Anesth Analg. 2002;95:385–8.

84. Raut CP, Hunt KK, Akins JS, Daley MD, Ross MI, Singletary SE,

et al. Incidence of anaphylactoid reactions to isosulfan blue dye

during breast carcinoma lymphatic mapping in patients treated with

preoperative prophylaxis: results of a surgical prospective clinical

practice protocol. Cancer. 2005;104:692–9.

85. Scherer K, Studer W, Figueiredo V, Bircher AJ. Anaphylaxis to

isosulfan blue and cross-reactivity to patent blue V: case report and

review of the nomenclature of vital blue dyes. Ann Allergy Asthma

Immunol. 2006;96:497–500.

86. Zanzonico P, Heller S. The intraoperative gamma probe: basic

principles and choices available. Semin Nucl Med. 2000;1:33–48.

87. International Electrotechnical Commission. Medical electrical equip-

ment –Part 1: General requirements for safety and essential perfor-

mance. IEC 60601-1 ed3.1 Geneva: IEC; 2012. https://webstore.iec.

ch/webstore/webstore.nsf/standards+ed/IEC%2060601-1%20Ed.%

203.1?OpenDocument (accessed March 2013).

Eur J Nucl Med Mol Imaging

88. Liu LC, Lang JE, Jenkins T, Lu Y, Ewing CA, Hwang SE, et al. Is it

necessary to harvest additional lymph nodes after resection of the

most radioactive sentinel lymph node in breast cancer? J Am Coll

Surg. 2008;207:853–8.

89. Chung A, Yu J, Stempel M, Patil S, Cody H, Montgomery L. Is the

“10% rule”equally valid for all subsets of sentinel-node-positive

breast cancer patients? Ann Surg Oncol. 2008;15:2728.

90. Clough KB, Nasr R, Nos C, Vieira M, Inguenault C, Poulet B. New

anatomical classification of the axilla with implications for sentinel

node biopsy. Br J Surg. 2010;97:1659–65.

91. Uren RF, Howman-Giles R, Chung DK, Spillane AJ, Noushi F,

Gillett D, et al. SPECT/CT scans allow precise anatomical location

of sentinel lymph nodes in breast cancer and redefine lymphatic

drainage from the breast to the axilla. Breast. 2012;21:480–6.

92. Aarsvold JN, Alazraki NP. Update on detection of sentinel lymph

nodes in patients with breast cancer. Semin Nucl Med. 2005;35:

116–28.

93. Serrano Vicente J, Infante de la Torre JR, Domínguez Grande ML,

García Bernardo L, Durán Barquero C, Rayo Madrid JI, et al.

Optimization of sentinel lymph node biopsy in breast cancer by

intraoperative axillary palpation. Rev Esp Med Nucl. 2010;29:8–11.

94. Cheng G, Kurita G, Kurita S, Torigian DA, Alavi A. Current status

of sentinel lymph-node biopsy in patients with breast cancer. Eur J

Nucl Med Mol Imaging. 2011;38:562–75.

95. Brenot-Rossi I, Houvenaeghel G, Jacquemier J, Bardou VJ, Martino

M, Hassan-Sebbag N, et al. Nonvisualization of axillary sentinel

node during lymphoscintigraphy: is there a pathologic significance

in breast cancer? J Nucl Med. 2003;44:1232–7.

96. Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S,

et al. Sentinel lymph node biopsy and axillary dissection in breast

cancer: results in a large series. J Natl Cancer Inst. 1999;91(4):368–

73.

97. Leidenius MH, Krogerus LA, Toivonen TS, Leppänen EA, von

Smitten KA. The sensitivity of axillary staging when using sentinel

node biopsy in breast cancer. Eur J Surg Oncol. 2003;29:849–53.

98. Goyal A, Newcombe RG, Mansel RE, Axillary Lymphatic Mapping

Against Nodal Axillary Clearance (ALMANAC) Trialists Group.

Clinical relevance of multiple sentinel nodes in patients with breast

cancer. Br J Surg. 2005;92:438–42.

99. Ban EJ, Lee JS, Koo JS, Park S, Kim SI, Park BW. How many

sentinel lymph nodes are enough for accurate axillary staging in T1-

2 breast cancer? J Breast Cancer. 2011;14:296–300.

100. Schuman S, Walker G, Avisar E. Processing sentinel nodes in breast

cancer: when and how many? Arch Surg. 2011;146:389–93.

101. Waddington WA, Keshtgar MRS, Taylor I, Lakhani SR, Short MD,

Ell PJ. Radiation safety of the sentinel node technique in breast

cancer. Eur J Nucl Med. 2000;27:377–91.

102. Krishnamurthy S, Meric-Bernstam F, Lucci A, Hwang RF, Kuerer

HM, Babiera G, et al. A prospective study comparing touch imprint

cytology, frozen section analysis, and rapid cytokeratin immuno-

stain for intraoperative evaluation of axillary sentinel lymph nodes

in breast cancer. Cancer. 2009;115:1555–62.

103. Bernet L, Cano R, Martinez M, Dueñas B, Matias-Guiu X, Morell

L, et al. Diagnosis of the sentinel lymph node in breast cancer: a

reproducible molecular method: a multicentric Spanish study.

Histopathology. 2011;58:863–9.

104. Bergqvist L, Strand SE, Persson B, Hafström L, Jönsson PE.

Dosimetry in lymphoscintigraphy of Tc-99m antimony sulfide col-

loid. J Nucl Med. 1982;23:698–705.

105. Cremonesi M, Ferrari M, Sacco E, Rossi A, De Cicco C, Leonardi

L, et al. Radiation protection in radioguidedsurgery of breast cancer.

Nucl Med Commun. 1999;20:919–24.

106. Law M, Cheng KC, Wu PM, Ho WY, Chow LW. Patient effective

dose from sentinel lymph node lymphoscintigraphy in breast can-

cer: a study using a female humanoid phantom and thermolumines-

cent dosimeters. Br J Radiol. 2003;76:818–23.

107. Law M, Chow LW, Kwong A, Lam CK. Sentinel lymph node

technique for breast cancer: radiation safety issues. Semin Oncol.

2004;31:298–303.

108. Sata S, Knesaurek K, Krynyckyi BR. Effective dose in sentinel

lymph node imaging. Br J Radiol. 2004;77:709. author reply

709.

109. Dubernard G, Garbay JR, Rouzier R, Delaloge S. Safety of sentinel

node biopsy in pregnant patients. Ann Oncol. 2005;16:987. author

reply 987–8.

110. Pandit-Taskar N, Dauer LT, Montgomery L, St Germain J,

Zanzonico PB, Divgi CR. Organ and fetal absorbed dose estimates

from 99mTc-sulfur colloid lymphoscintigraphy and sentinel node

localization in breast cancer patients. J Nucl Med. 2006;47:1202–8.

111. Miner TJ, Shriver CD, Flicek PR, Miner FC, Jaques DP,

Maniscalco-Theberge ME, et al. Guidelines for the safe use of

radioactive materials during localization and resection of the senti-

nel lymph node. Ann Surg Oncol. 1999;6:75–82.

112. Stratmann SL, McCarty TM, Kuhn JA. Radiation safety with breast

sentinel node biopsy. Am J Surg. 1999;178:454–7.

113. Morton R, Horton PW, Peet DJ, Kissin MW. Quantitative assess-

ment of the radiation hazards and risks in sentinel node procedures.

Br J Radiol. 2003;76:117–22.

114. de Kanter AY, Arends PP, Eggermont AM, Wiggers T. Radiation

protection for the sentinel node procedure in breast cancer. Eur J

Surg Oncol. 2003;29:396–9.

115. Klausen TL, Chakera AH, Friis E, Rank F, Hesse B, Holm S.

Radiation doses to staff involved in sentinel node operations for

breast cancer. Clin Physiol Funct Imaging. 2005;25:196–202.

116. Nejc D, WrzesieńM, Piekarski J, Olszewski J, Pluta P, Kuśmierek J,

et al. Sentinelnode biopsy in patients with breast cancer –evaluation

of exposure to radiation of medical staff. Eur J Surg Oncol. 2006;32:

133–8.

117. Glass EC, Waddington WA. Radiation protection in radioguided

surgery, chapter 5. In: Mariani G, Giuliano AE, Strauss HW, editors.

Radioguided surgery: a comprehensive team approach. Springer

Science+Business Media, LLC; 2008. p. 37–47.

118. Glass EC, Basinski JE, Krasne DL, Giuliano AE. Radiation safety

considerations for sentinel node techniques. Ann Surg Oncol.

1999;6:10–1.

119. Singleton M, Firth M, Stephenson T, Morrison G, Baginska J.

Radiation-guided breast sentinel lymph node biopsies –is a han-

dling delay for radiation protection necessary? Histopathology.

2012;61:277–82.

120. Nanocoll package insert, 2012. http://www.produktresume.dk/

docushare/dsweb/GetRendition/Document-13422/html (accessed

March 2013).

121. Pharmalucence, Inc., package insert for 99mTc sulfur colloid, 2012.

http://www.sulfurcolloid.com/pdf/PI.pdf (accessed March 2013).

122. Clarke RH, Bines W. Evolution of ICRP Recommendations 1977,

1990, 2007 –Publications 26 to 60 to 103. OECD NEA, No 6920,

2011. http://www.oecd-nea.org/rp/reports/2011/nea6920-ICRP-

recommendations.pdf.

123. Spanheimer PM, Graham MM, Sugg SL, Scott-Conner CE,

Weigel RJ. Measurement of uterine radiation exposure from

lymphoscintigraphy indicates safety of sentinel lymph node biopsy

during pregnancy. Ann Surg Oncol. 2009;16:1143–7.

124. United States Nuclear Regulatory Commission. NRC regulatory

issue summary 2008-31 licensing requirements for sentinel lymph

node biopsy. 2008. http://pbadupws.nrc.gov/docs/ML0816/

ML081620152.pdf (accessed March 2013).

125. Keshtgar MRS, Waddington WA, Lakhani SR, Ell PJ. Dosimetry

and radiation protection. In: Keshtgar MRS, Waddington WA,

Lakhani SR, Ell PJ, editors. The sentinel node in surgical oncology.

Berlin: Springer; 1999.

126. Law M, Ma WH, Leung R, Li S, Wong KK, Ho WY, et al. Evaluation

of patient effective dose from sentinel lymph node

Eur J Nucl Med Mol Imaging

lymphoscintigraphy in breast cancer: a phantom study with SPECT/

CT and ICRP-103 recommendations. Eur J Radiol. 2012;81:717–20.

127. Veronesi U, Galimberti V, Paganelli G, Maisonneuve P, Viale G,

Orecchia R, et al. Axillary metastases in breast cancer patients with

negative sentinel nodes: a follow-up of 3548 cases. Eur J Cancer.

2009;45:1381–8.

128. Meretoja TJ, Leidenius MH, Heikkilä PS, Joensuu H. Sentinel node

biopsy in breastcancer patients with large or multifocal tumors. Ann

Surg Oncol. 2009;16:1148–55.

129. Kumar R, Jana S, Heiba SI, Dakhel M, Axelrod D, Siegel B, et al.

Retrospective analysis of sentinel node localization in multifocal

multicentric, palpable, or non palpable breast cancer. J Nucl Med.

2003;44:7–10.

130. Spillane AJ, Brennan ME. Accuracy of sentinel lymph node biopsy

in large and multifocal/multicentric breast carcinoma –a systematic

review. Eur J Surg Oncol. 2011;37:371–85.

131. Gentilini O, Veronesi P, Botteri E, Soggiu F, Trifirò G, Lissidini G,

et al. Sentinel lymph node biopsy in multicentric breast cancer: five-

year results in a large series from a single institution. Ann Surg

Oncol. 2011;18:2879–84.

132. IntraM, Rotmensz N, Veronesi P, Colleoni M, Iodice S,Paganelli G,

et al. Sentinel node biopsy is not a standard procedure in ductal

carcinoma in situ of the breast: the experience of the European

Institute of Oncology on 854 patients in 10 years. Ann Surg.

2008;247:315–9.

133. Taback B, Nguyen P, Hansen N, Edwards GK, Conway K, Giuliano

AE. Sentinel lymph node biopsy for local recurrence of breast

cancer after breast-conserving therapy. Ann Surg Oncol. 2006;13:

1099–104.

134. Specht MC, Fey JV, Borgen PI, Cody 3rd HS. Is the clinically

positive axilla in breast cancer really a contraindication to sentinel

lymph node biopsy? J Am Coll Surg. 2005;200:10–4.

135. Paganelli G, Galimberti V, Trifirò G, Travaini L, De Cicco C,

Mazzarol G, et al. Internal mammary node lymphoscintigraphy

and biopsy in breast cancer. Q J Nucl Med. 2002;46:138–44.

136. Krynyckyi BR, Chun H, Kim HH, Eskandar Y, Kim CK,

Machac J. Factors affecting visualization rates of internal

mammary sentinel nodes during lymphoscintigraphy. J Nucl

Med. 2003;44:1387–93.

137. Estourgie SH, Tanis PJ, Nieweg OE, Valdés Olmos RA, Rutgers EJ,

Kroon BB. Should the hunt for internal mammary chain sentinel

nodes begin? An evaluation of 150 breast cancer patients. Ann Surg

Oncol. 2003;10:935–41.

138. Paredes P, Vidal-Sicart S, Zanón G, Pahisa J, Fernández PL, Velasco

M, et al. Clinical relevance of sentinel lymph nodes in the internal

mammary chain in breast cancer patients. Eur J Nucl Med Mol

Imaging. 2005;32:1283–7.

139. Bourre JC, Payan R, Collomb D, Gallazzini-Crepin C, Calizzano A,

Desruet MD, et al. Can the sentinel lymph node technique affect

decisions to offer internal mammary chain irradiation? Eur J Nucl

Med Mol Imaging. 2009;36:758–64.

140. Veronesi U, Marubini E, Mariani L, Valagussa P, Zucali R. The

dissection of internal mammary nodes does not improve the survival

of breast cancer patients. 30-year results of a randomised trial. Eur J

Cancer. 1999;35:1320–5.

141. Noushi F, Spillane AJ, Uren RF, Gebski V. Internal mammary node

metastasis in breast cancer: predictive models to determine status

and management algorithms. Eur J Surg Oncol. 2010;36:16–22.

142. Leidenius MH, Krogerus LA, Toivonen TS, Leppänen EA, von

Smitten KA. The clinical value of parasternal sentinel node biopsy

in breast cancer. Ann Surg Oncol. 2006;13:321–6.

143. LuiniA, Galimberti V, Gatti G, Arnone P, Vento AR, Trifiro G, et al.

The sentinel node biopsy after previous breast surgery; preliminary

results on 543 patients treated at EIO. Breast Cancer Res Treat.

2005;89:159–63.

144. Leidenius MH, Vironen JH, von Smitten KA, Heikkilä PS,

Joensuu HJ. The outcome of sentinel node biopsy in breast

cancer patients with preoperative surgical biopsy. Surg Oncol.

2009;99:420–3.

145. Rodriguez Fernandez J, Martella S, Trifirò G, Caliskan M, Chifu C,

Brenelli F, et al. Sentinel node biopsy in patients with previous

breast aesthetic surgery. Ann Surg Oncol. 2009;16:989–92.

146. Kothari MS, Rusby JE, Agusti AA, MacNeill FA. Sentinel lymph

node biopsy after previous axillary surgery: a review. Eur J Surg

Oncol. 2012;38:8–15.

147. Veronesi P, Gentilini O, Rodriguez-Fernandez J, Magnoni F. Breast

conservation and sentinel lymph node after neoadjuvant systemic

therapy. Breast. 2009;18:590–2.

148. Mamounas EP, Brown A, Anderson S, Smith R, Julian T,

Miller B, et al. Sentinel node biopsy after neoadjuvant chemo-

therapy in breast cancer: results from National Surgical Adjuvant

Breast and Bowel Project Protocol B-27. J Clin Oncol. 2005;23:

2694–702.

149. Kelly AM, Dwamena B, Cronin P, Carlos RC. Breast cancer senti-

nel node identification and classification after neoadjuvant chemo-

therapy –systematic review and metaanalysis. Acad Radiol.

2009;16:551–63.

150. Schwartz GF, Meltzer AJ. Accuracy of sentinel node biopsy follow-

ing neoadjuvant (induction) chemotherapy for carcinoma of the

breast. Breast J. 2003;9:374–9.

Eur J Nucl Med Mol Imaging

Diagnosis and Management of Cancers in Pregnancy: The Results of a Dual Battle Between Oncological Condition and Maternal Environment—Literature Review

Article

Full-text available

Jan 2025

Cancer during pregnancy presents considerable challenges that arise from various factors, including the diagnostic, prognostic and therapeutic implications of managing cancer in this unique patient population. There is a crucial need for an integrated approach that aligns medical interventions for both the pregnant patient and the developing embryo or fetus. Furthermore, the distinct characteristics associated with each stage of gestation may significantly influence the treatment protocols that can be proposed. Due to all of these factors, the importance of collaboration among healthcare professionals from different specialties (to ensure that both mother and child receive optimal care throughout the pregnancy) is often neglected. This review is designed to provide a thorough overview of the current standard procedures regarding the diagnosis and treatment options for cancer in pregnant patients in order to ensure the safety of mother and child. Furthermore, the review describes the feasibility of current fertility preservation methods, highlights the psychological effects of cancer during pregnancy and examines the risks and benefits of breastfeeding.

Heterogeneous Distribution and Absorbed Dose of Radiolabeled Nanoparticles and Colloids in Sentinel Lymph Nodes

Article

Full-text available

Feb 2025
CANCER BIOTHER RADIO

Background: For breast cancer staging, radiolabeled colloids and superparamagnetic iron oxide nanoparticles (SPIONs) are used for sentinel lymph node (SLN) imaging. This study characterized the intranodal activity distribution and absorbed dose distribution. Material and Methods: Six patients diagnosed with primary breast cancer were intradermally injected with 99mTc-Nanocoll. The SLNs were resected, weighed, and measured for activity. Three groups of six rats were subcutaneously injected into the hind paw with either 99mTc-Nanocoll, 99mTc-SPIONs, or 68Ga-SPIONs. Macro- and small-scale dosimetry calculations were performed using autoradiography images of cryosections of SLNs from patients and animals. Results: The mean absorbed dose in patient SLNs was 0.5 ± 0.3 mGy/MBq for 99mTc-Nanocoll and 3.4 ± 1.8 mGy/MBq, assuming a 99mTc-Nanocoll-based distribution of 68Ga-SPIONs. Due to different decay characteristics, the heterogeneity in the absorbed dose differed between 99mTc-SPIONs and 68Ga-SPIONs with a maximum to mean absorbed dose ratio of 2.7 ± 0.3 and 1.6 ± 0.2, respectively. Conclusions: This study shows that 99mTc- and 68Ga-SPIONs and 99mTc-nanocolloids have similar activity distribution in human and animal lymph nodes. Small-scale dosimetry models combined with clinical patient biokinetics may serve as a bridge between organ and tissue dosimetry and the interpretation of intrinsic geometric variation and its uncertainties in absorbed dose.

Early-stage oral cavity cancer (T1N0) with lymphatic drainage to the retropharyngeal lymph node: A therapeutic challenge

Article

Jan 2025

Iterative reconstruction of SiPM light response functions in a square-shaped compact gamma camera

Preprint

Oct 2016

Compact gamma cameras with a square-shaped monolithic scintillator crystal and an array of silicon photomultipliers (SiPMs) are actively being developed for applications in areas such as small animal imaging, cancer diagnostics and radiotracer guided surgery. Statistical methods of position reconstruction, which are potentially superior to the traditional centroid method, require accurate knowledge of the spatial response of each photomultiplier. Using both Monte Carlo simulations and experimental data obtained with a camera prototype, we show that the spatial response of all photomultipliers (light response functions) can be parameterized with axially symmetric functions obtained iteratively from flood field irradiation data. The study was performed with a camera prototype equipped with a 30 x 30 x 2 mm3 LYSO crystal and an 8 x 8 array of SiPMs for 140 keV gamma rays. The simulations demonstrate that the images, reconstructed with the maximum likelihood method using the response obtained with the iterative approach, exhibit only minor distortions: the average difference between the reconstructed and the true positions in X and Y directions does not exceed 0.2 mm in the central area of 22 x 22 mm2 and 0.4 mm at the periphery of the camera. A similar level of image distortions is shown experimentally with the camera prototype.

Radiotracers for Imaging of Breast Cancer and Targeted Radionuclide Therapy

Chapter

Jun 2025

Targeted Radiopharmaceutical Therapy (RPT) is emerging as an innovative approach for treating a wide range of cancers. Almost all radionuclides used in RPT emit photons that can be imaged, enabling non-invasive visualization of the therapeutic agent's biodistribution. The remarkable potential of radiopharmaceutical therapy is now being recognized with recent FDA approval of several RPT drugs and a significant number of drug candidates in clinical development. This book offers a comprehensive perspective on the different technologies and addresses the critical challenges in developing and commercializing radiopharmaceuticals. It covers various topics, from clinical applications to specific radiopharmaceutical biodistribution, dosimetry, and novel targets in oncology. The chapters provide a cohesive picture of the advances in SPECT/CT and PET/CT imaging, clinical trends in targeted therapies utilizing radioisotopes for cancer imaging, and clinical applications of radiotracers within oncology areas. It also delves into the manufacturing technologies and regulatory and supply logistics required to support the development of the next wave of targeted alpha therapies. This resource is ideal for postgraduates and researchers in drug discovery and development in radionuclide therapy and imaging in cancer, as well as medical professionals engaged in nuclear medicine and radiology.

Imagerie nucléaire du cancer du sein

Article

Jan 2023

V. Roux

Technique et indications du ganglion sentinelle dans la chirurgie des tumeurs cutanées

Article

Jul 2020

Evaluation of diagnostic value of [67Ga]Ga-phytate in detection of axillary lymph nodes in breast cancer patients

Article

Jan 2025
J RADIOANAL NUCL CH

99mTc has been accepted as an ideal radionuclide for lymphoscintigraphy. Nevertheless, the need for another radionuclide with different half-life and photo-peak is required, particularly in research settings to differentiate the root of lymphatic drainage for 2 different injection sites as well as scenarios when longer half-life would be a privilege. In his study diagnostic value of a new radiotracer ([67Ga]Ga-phytate) for lymphoscintigraphy to determine sentinel lymph nodes (SLNs) in patients with breast cancer will be discussed. This pilot study recruited 10 female patients with breast cancer aged 49.7 years who were referred for pre-surgical lymphoscintigraphy. The patients underwent two injections of [67Ga]Ga-phytate and single photon emission computed tomography imaging procedure. This was followed by injection of blue dye. During the surgery both gamma probe and colorimetry were used for evaluation and dissection of involved sentinel lymph nodes. The final results were investigated by an expert pathologist. Diagnosis of sentinel lymph nodes was accomplished in 100% and 90% of patients with [67Ga] Ga-phytate and blue dye, respectively. Totally 19 sentinel lymph nodes were detected in 10 patients (1.9 per patient) with [67Ga]Ga-phytate. Out of all, in 50% of patients the detected sentinel lymph nodes had tumor involvement which 40% was macro-metastasis. Besides, among all the detected sentinel lymph nodes, 35 of them were diagnosed and dissected of which only one was found metastatic. Based on our findings [67Ga]Ga-phytate has excellent performance for detection of sentinel lymph nodes in breast cancer patients and this tracer could be used in certain circumstances particularly when longer time intervals is required between the lymphoscintigraphy and surgery procedure as an efficient alternative for [99mTc]Tc-phytate. Furthermore, this tracer could be used in research settings with different lymphatic drainage basins.

Is preoperative imaging of sentinel lymph node in breast cancer necessary? A retrospective case control study

Article

Dec 2024
BREAST

Objective The necessity of preoperative lymphoscintigraphy before intraoperative sentinel lymph node (SLN) identification is still unclear. The aim of the present study was to evaluate the impact of SLN imaging on intraoperative SLN detection in breast cancer patients. Methods Retrospective, comparative, single center study of patients with breast cancer stage pT1 and pT2 who underwent axillary staging. Group 1 included patients who underwent SLN extirpation without preoperative SLN imaging, and Group 2 included patients who underwent SLN imaging prior to surgery. Differences between groups were analyzed using T-test and chi-square test. Results 926 (mean age: 61.45 years) patients received subdermal injection of radiolabeled nanocolloids between tumor and axilla. SLN was identified intraoperatively in 473 of 498 patients (94.98 %) in group 1, and in 415 of 428 patients (96.96 %) in group 2 (p = 0.129). Lymphoscintigraphy detected SLN in 407 of 428 (95.09 %) patients in group 2. Due to the additional SLN imaging in group 2, the time between radiotracer injection and start of surgery was significantly prolonged (p < 0.001). A reduction of applied activity from a median of 18 MBq in group 1 to a median of 12 MBq in group 2 had no negative effect on the SLN identification. Conclusion Subdermal injection of radiolabeled nanocolloids between tumor and axilla allowed high intraoperative detection of SLN. Preoperative SLN imaging had no significant impact on the intraoperative detection but is a time-consuming and resource-intensive procedure. Prospective studies might provide further evidence to omit preoperative SLN imaging in patients with T1-2 invasive breast cancer and clinically negative axilla.

Oncology

Chapter

Nov 2024

Nuclear medicine offers various studies to detect cancer foci, staging cancer, assessing response to treatments, and various other indications. In this section, common radionuclide cancer imaging studies and normal image patterns will be summarized for practical use. Various oncologic case studies will be presented.

Radioguided Surgery: A Comprehensive Team Approach

Book

Jan 2008

Radioguided Surgery is a multidisciplinary book designed for all physicians involved in the diagnosis and care of cancer patients, including nuclear medicine physicians, general surgeons, oncologists, and pathologists. The contributors to this book—among them some of the most prestigious experts in the field—provide comprehensive coverage of all aspects of radioguided surgery, from training and radiation protection to sentinel lymph node biopsy and non-sentinel lymph node applications for various cancers, tumors and lesions. More than a hundred illustrations, including a full-color insert, help to facilitate understanding of new concepts. Given its depth of information and concise, clear presentation, Radioguided Surgery is an indispensable resource in this innovative and increasingly integral field.

Advances in the surgical management of early stage invasive breast cancer

Article

Nov 2004
CURR PROB SURG

A synthetic macromolecule for sentinel node detection: Tc-99m-DTPA-mannosyl-dextran

Article

Jun 2001

We report the synthesis and preliminary biologic testing of a synthetic macromolecule, Tc-99m-diethylenetriaminepentaacetic acid (DTPA)-mannosyl-dextran, for sentinel node detection. Methods: Synthesis started with a P-step process that attaches a high density of amino-terminated leashes to a dextran backbone. Allyl-bromide was reacted with pharmaceutical-grade dextran to yield allyl-dextran. After diafiltration with water, filtration, and lyophilization, the product was reacted with aminoethanethiol and ammonium persulfate. The resulting amino-conjugated dextran was dialyzed, filtered, and lyophilized. The mixed anhydride method was used to attach DTPA; after dialysis, filtration, and lyophilization, 2-imino-2-methoxyethyl-1-D-mannose was used to attach the receptor substrate. The molecular diameter was measured by dynamic light scattering. Amino, mannose, and DTPA densities were measured by trinitrobenzene sulfonate assay, sulfuric acid/phenol assay, and inductively coupled plasma spectroscopy of gadolinium-DTPA-mannosyl-dextran, respectively. Receptor affinity was measured by Scatchard assay of rabbit liver. Axillary, popliteal, and iliac lymph nodes and each injection site were assayed for radioactivity at 1 and 3 h after injection of approximately 3.7 MBq (0.050 mt) Tc-99m-DTPA-mannosyl-dextran (0.22 nmol) or filtered Tc-99m-sulfur colloid into the foot pads. Four animals were studied at each time point. Results: DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a molecular diameter of 7.1 nm. The final amine, mannose, and DTPA densities were 23, 55, and 8 mol per dextran. Labeling yields were in excess of 98% and stable for 6 h. Specific activities of 74 x 10(6) GBq/mol were achieved. The equilibrium dissociation constant for binding to the mannose-terminated glycoprotein receptor was 0.12 +/- 0.07 nmol/L. The popliteal extraction at both 1 h and 3 h was significantly (P < 0.05) higher for Tc-99m-DTPA-mannosyl-dextran (90.1% +/- 10.7% and 97.7% +/- 2.0%, respectively) than for filtered Tc-99m-sulfur colloid (78.8 +/- 6.5 and 67.4% +/- 26.8%, respective ly). Tc-99m-DTPA-mannosyl-dextran exhibited significantly faster injection site clearance than did filtered Tc-99m-sulfur colloid. The Tc-99m-DTPA-mannosyl-dextran percentage injected dose (%ID) for the front and rear paws was 52.6 +/- 10.5 and 52.3 +/- 8.0 at 1 h and 45.7 +/- 8.5 and 43.6 +/- 8.2 at 3 h after administration. The filtered Tc-99m-sulfur colloid %ID for the front and rear paws was 70.4 +/- 11.0 and 66.3 +/- 15.1 at 1 h and 55.5 +/- 7.8 and 66.9 +/- 8.5 at 3 h. Lymph node accumulation of each agent at either 1 or 3 h was not significantly different. Conclusion: Tc-99m-DTPA-mannosyl-dextran is a receptor-based sentinel node radiotracer that exhibits the desired properties of rapid injection site clearance and low distal node accumulation. This molecule is the first member of a new class of diagnostic agents based on a macromolecular backbone with a high density of sites for the attachment of substrates and imaging reporters.

Radiation safety for the sentinel lymph node technique in breast cancer

Article

Sep 1999
Eur J Nucl Med

Sentinel node biopsy in breast cancer: Increased feasibility by using 10 mCi radiocolloid in combination with a blue dye tracer.

Article

Apr 1999
Eur J Nucl Med

The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-Year results of a randomised trial

Article

Jan 1990
EUR J CANCER

American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer

Article

Jan 2005

Sentinel-Node Biopsy to Avoid Axillary Dissection in Breast Cancer with Clinically Negative Lymph-Nodes

Article

Jan 1998

Background. Axillary lymph-node dissection is an important staging procedure in the surgical treatment of breast cancer. However, early diagnosis has led to increasing numbers of dissections in which axillary nodes are free of disease. This raises first, questions about the need for the procedure. We carried out a study to assess, first, whether a single axillary lymph node (sentinel node) initially receives malignant cells from a breast carcinoma and, second, whether a clear sentinel node reliably forecasts a disease-free axilla.

Preliminary technical results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer patients

Article

Jan 2004

LBA505 Background: NSABP B-32 is the largest prospective randomized phase III trial designed to determine in SN negative patients that SNR alone results in the same survival and regional control as SNR + AD while reducing morbidity. It was designed to detect a survival difference of 2% between the 2 groups at 5 years. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group 1) or to SNR alone with AD only if SNs were positive (Group 2). 3,989 (71.1%) of the 5,611 patients were SN negative and followed for events. 99.9% of these SN negative patients had follow-up information: 1,975 in Group 1 and 2,011 in Group 2. Median time on study was 95.3 months. Patients were well balanced across clinical strata. Log-rank tests for unadjusted analyses and Cox proportional hazard models adjusting for study stratification variables were used to compare overall survival (OS) and disease-free survival (DFS) between the two groups. Two-sided p-values were used. HR values > 1 indicate a more favorable outcome in Group 1 (SNR + AD). Results: Comparisons of OS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.20 (p = 0.12) and an adjusted HR of 1.19 (p=0.13). Five-year Kaplan-Meier estimates for OS are 96.4% in Group 1 and 95.0% in Group 2 and the 8-year estimates are 91.8% and 90.3%, respectively. Comparisons of DFS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.05 (p=0.54) and an adjusted HR of1.07 (p=0.57). No substantial differences could be seen across sites for first treatment failure. Five-year Kaplan-Meier estimates for DFS are 89.0% in Group 1, and 88.6% in Group 2 and the 8-year estimates are 82.4% and 81.5%, respectively. Local and Regional Recurrences: There were 54 local recurrences in Group 1 and 49 in Group 2 (p=0.55). There were 8 regional node recurrences as first events in Group 1 and 14 in Group 2 (p=0.22). Conclusions: No significant differences were observed in OS, DFS, or regional control between the trial groups. Within the limits of this trial, SNR without AD is validated as a safe and effective method for regional node treatment of SN negative breast cancer patients. [Table: see text]

Image-Detected Breast Cancer: State of The Art Diagnosis and Treatment

Article

Sep 2001

The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer

Abstract and Figures

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