Lymphatic mapping and sentinel node biopsy in ovarian tumors: A study using intra-operative Tc-99m-Phytate and lymphoscintigraphy imaging

Abstract

Background
Experience on sentinel node mapping in ovarian tumors is very limited. We evaluated the sentinel node concept in ovarian tumors using intra-operativeTc-99m-Phytate injection and lymphoscintigraphy imaging.

Methods
Thirty-five patients with a pelvic mass due to an ovarian pathology were included in the study. The radiotracer was injected just after laparotomy and before removal of the tumor either beneath the normal cortex (10 patients) or in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum two injections of the radiotracer (25 patients). For malignant masses, the sentinel nodes were identified using a hand held gamma probe. Then standard pelvic and para-aortic lymphadenectomy was performed. In case of benign pathologies or borderline ovarian tumors on frozen section, lymphadenectomy was not performed. The morning after surgery, all patients were sent for lymphoscintigraphy imaging of the abdomen and pelvis.

Results
Sentinel node was identified only in 4 patients of the cortical injection group. At least one sentinel node could be identified in 21 patients of the sub-peritoneal group. Sentinel nodes were identified only in the para-aortic area in 21, pelvic/para-aortic areas in 2, and pelvic only area in 2 patients. Three patients had lymph node involvement and all had involved sentinel nodes (no false negative case).

Conclusion
Sentinel node mapping using intra-operative injection of the radiotracer (in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum) is feasible in ovarian tumors. Technical aspects of this method should be explored in larger multicenter studies in the future.

Full text

R E S E A R C H Open Access
Lymphatic mapping and sentinel node
biopsy in ovarian tumors: a study using
intra-operative Tc-99m-Phytate and
lymphoscintigraphy imaging
Malihe Hassanzadeh
1
, Elham Hosseini Farahabadi
1
, Zohreh Yousefi
1
, Sima Kadkhodayan
1
, Leili Zarifmahmoudi
2
and Ramin Sadeghi
2*
Abstract
Background: Experience on sentinel node mapping in ovarian tumors is very limited. We evaluated the sentinel
node concept in ovarian tumors using intra-operativeTc-99m-Phytate injection and lymphoscintigraphy imaging.
Methods: Thirty-five patients with a pelvic mass due to an ovarian pathology were included in the study. The
radiotracer was injected just after laparotomy and before removal of the tumor either beneath the normal cortex
(10 patients) or in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum two
injections of the radiotracer (25 patients). For malignant masses, the sentinel nodes were identified using a hand
held gamma probe. Then standard pelvic and para-aortic lymphadenectomy was performed. In case of benign
pathologies or borderline ovarian tumors on frozen section, lymphadenectomy was not performed. The morning
after surgery, all patients were sent for lymphoscintigraphy imaging of the abdomen and pelvis.
Results: Sentinel node was identified only in 4 patients of the cortical injection group. At least one sentinel node
could be identified in 21 patients of the sub-peritoneal group. Sentinel nodes were identified only in the para-aortic
area in 21, pelvic/para-aortic areas in 2, and pelvic only area in 2 patients. Three patients had lymph node
involvement and all had involved sentinel nodes (no false negative case).
Conclusion: Sentinel node mapping using intra-operative injection of the radiotracer (in the utero-ovarian and
suspensory ligaments of the ovary just beneath the peritoneum) is feasible in ovarian tumors. Technical aspects of
this method should be explored in larger multicenter studies in the future.
Keywords: Ovary, Ovarian tumor, Sentinel, Lymphoscintigraphy, Lymphatic mapping, Blue dye
Background
Epithelial ovarian cancer is the most common ovarian
malignancy and is the leading cause of death from
gynecological cancers in the United States [1, 2]. About
a third of epithelial ovarian cancers presents in an early
stage [3]. Para-aortic and pelvic lymph node dissection is
the recommended procedure for lymph node staging of
epithelial ovarian cancers [4]. However routine lymph
node dissection did not show any survival benefit even
in advanced ovarian cancers [5]. Incidence of lymph
node involvement in the early ovarian cancers (stage I)
is also low (about 10–20 %) [6] and majority of patients
with early ovarian cancer would not benefit from routine
lymphadenectomy while being subject to its unwanted
consequences such as prolonged hospitalization, more
blood loss, and longer surgical time [7, 8].
In the last two decades, sentinel node mapping has
been introduced to the surgical management of many
solid tumors. Although lymphatic mapping has been ap-
plied successfully for gynecological and urological can-
cers [9–14], it has not been adequately evaluated for
ovarian cancers in the medical literature: To the extent
* Correspondence: sadeghir@mums.ac.ir;raminsadeghi1355@yahoo.com
2
Nuclear Medicine Research Center, Mashhad University of Medical Sciences,
Mashhad, Iran
Full list of author information is available at the end of the article
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Hassanzadeh et al. Journal of Ovarian Research (2016) 9:55
DOI 10.1186/s13048-016-0265-4
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

of our knowledge only four studies thus far is available
in this regard [15–18].
In the current study, we evaluated the sentinel node
concept in ovarian tumors using intra-operativeTc-99m-
Phytate injection and lymphoscintigraphy imaging.
Methods
During a period from Jan 2010 to Oct 2014, 35 patients
with a pelvic mass diagnosed to be due to an ovarian
pathology were eligible to be included in the study. All
patients provided written informed consent before en-
rollment in the study, and the study was approved by
the Local Ethical Committee of Mashhad University of
Medical Sciences under the approval number of 931331.
Pregnant or lactating patients, patients with the history
of previous surgery on one or both ovaries; previous
lymph node surgery in the pelvic or para-aortic areas; a
history of any malignant tumor in the abdominal or pel-
vic cavities were excluded from the study.
Sentinel node mapping
We used Tc-99m-Phytate for lymphatic mapping in all
patients. The radiotracer was injected just after laparot-
omy and before removal of the tumoral ovary. The first
10 patients received two injections of the radiotracer
(1 mCi/0.2 mL/injection) beneath the normal cortex of
the ovary. The remainder of the patients received two
injections of the radiotracer (1 mCi/0.2 mL each) in the
utero-ovarian and suspensory ligaments of the ovary just
beneath the peritoneum close to the diseased ovary
(Fig. 1). In four patients of the second group, patent blue
V dye was also injected in the same location as the ra-
diotracer (0.2 cc/injection).
The surgeon waited for 10 min interval before removal
of the adnexal mass in order to give the radiotracer
enough time to move in the lymphatics. The adnexal mass
was then sent to the pathologist for frozen section
evaluation. For malignant masses, the sentinel nodes were
identified using a hand held gamma probe (EUROPROBE,
Lyon, France) by searching the para-aortic and pelvic
areas. Any lymph node with 3 times more count than the
background was considered a sentinel node and was har-
vested separately for histopathological evaluation using
H&E staining. Then standard pelvic and para-aortic
lymphadenectomy was performed.
In case of benign pathologies or borderline ovarian tu-
mors on frozen section, lymphadenectomy was not per-
formed. However the gamma probe was used to locate
any hot area in the pelvic and par-aortic areas and the
locations of any hot spots were recorded.
The morning after surgery, all patients were sent to
the nuclear medicine ward for lymphoscintigraphy im-
aging of the abdomen and pelvis. Anterior and lateral
views (5 min/image) of the abdomen and pelvis were
taken by a dual head variable angle gamma camera
(E.CAM,SIEMENS,Germany)equippedwithlowen-
ergy all-purpose collimator and Tc-99m photopeak
[19]. The images were interpreted by two nuclear
medicine specialists familiar with sentinel node map-
ping and the results were correlated with the intra-
operative findings.
Results
Overall 35 patients entered the study. Table 1 shows the
characteristics of the patients. Ten patients had cortical
injection of the tracer (3 with malignant and 7 with be-
nign ovarian pathology). Sentinel node was identified
only in 4 patients of this group which amounts to 40 % de-
tection rate (2 with benign and 2 with malignant pathology).
Twenty-five patients received sub-peritoneal ligament injec-
tion of the mapping material (10 with malignant, one with
borderline pathology and 13 with benign pathology). At
least one sentinel node could be identified in 21 patient of
Fig. 1 Radiotracer injection in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum
Hassanzadeh et al. Journal of Ovarian Research (2016) 9:55 Page 2 of 8
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Table 1 Characteristics of the included patients
N Age/tumor side/tumor
size (cm)
Injection
location
Final pathological
results
Number and location of sentinel
nodes on lymphoscintigraphy findings
Comments
1 28/left/12 × 8 L Benign follicular cyst Two/para-aortic –
2 16/right/7 × 7 C Struma ovarii Three/para-aortic –
3 54/left/20 × 25 L Serous cysadenofibroma One/para-aortic –
4 35/left/10 × 9 L Mature teratoma Two/para-aortic –
5 45/left/20 × 15 C Granulosa cell tumor No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: Two hot sentinel nodes
were identified during surgery in the para-aortic
area. Sentinel nodes were not involved. No
other lymph node involvement.
6 42/right/15 × 10 L Mature teratoma with
ovarian torsion
None –
7 51/left/10 × 10 L Benign papillary serous
cyst with ovarian torsion
None –
8 17/left/7 × 7 L Benign serous cyst Two/para-aortic –
9 26/left/10 × 5 L Benign luteal cyst One/para-aortic –
10 32/right/8 × 10 L Mucinous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: Three hot sentinel nodes
were identified during surgery in the
para-aortic area. None were involved.
No lymph node involvement.
11 52/right/12 × 15 L Borderline serous
cystadenoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: One hot sentinel node
was identified during surgery in the
para-aortic area. None were involved.
No lymph node involvement.
12 59/right/6 × 8 C Mature teratoma Two/para-aortic –
13 56/right/12 × 9 C Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: No hot sentinel node was
identified during surgery in the para-aortic
area. No lymph node involvement.
14 36/left/7 × 6 L Mature teratoma with
ovarian torsion
None –
15 47/right/5 × 7 L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: Two hot sentinel nodes
was identified during surgery in the para-aortic
(one) and pelvic areas (one in the internal iliac
area). None were involved. No lymph
node involvement.
16 42/right/12 × 13 C Thechoma One/Para-aortic –
17 31/right/6 × 6 L Benign serous cyst One/Para-aortic –
18 42/right/6 × 8 C Benign mucinous
cystadenoma with
ovarian torsion
None –
19 60/Bilateral/10 × 8;6 × 8 L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: Three hot sentinel nodes
was identified during surgery in the para-aortic
(two) and pelvic areas (one in the obturator).
Both were involved. No other lymph node
involvement.
20 42/right/10 × 10 C Benign mucinous
cystadenoma
None –
21 68/left/6 × 8 L Benign mucinous
cystadenoma
One/Para-aortic –
22 40/left/6 × 8 L Benign mucinous
cystadenoma
One/Para-aortic –
23 26/left/6 × 5 C Granulosa cell tumor No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: The hot sentinel node
was identified during surgery in the
para-aortic area. Sentinel node was not
involved. No other lymph node involvement.
Hassanzadeh et al. Journal of Ovarian Research (2016) 9:55 Page 3 of 8
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this group which amounts to 84 % detection rate (11 with
malignant and 10 with benign pathology).
Four patients had ovarian torsion in addition to their
underlying pathology in the ovary. No sentinel node
could be identified in these patients.
Sentinel nodes were identified only in the para-aortic
area in all 12 patients with benign pathology and suc-
cessful lymphatic mapping. Sentinel nodes were identi-
fied in para-aortic area in 9 and pelvic/para-aortic areas
in 2 patients and pelvic only area in 2 patients with ma-
lignant pathology.
In four patients who received blue dye injection in
addition to radiotracer, all sentinel nodes were hot/blue.
Figure 2 shows a blue para-aortic sentinel node in one
of these patients.
Three patients with malignant pathology had lymph
node involvement and all had involved sentinel nodes on
pathology (100 % sensitivity and no false negative case).
No adverse reaction to the radiotracer or blue dye was
observed in our patients.
Figure 3 shows lymphoscintigraphy images of patient
number 8.
Discussion
Thus far, only limited studies on lymphatic mapping in
ovarian cancer have been published. Table 2 summarizes
the data of these studies in addition to the current one.
Two studies were done on normal ovaries of patients
who underwent laparotomy for other reasons [15, 16].
Both studies reported a high sentinel node detection
rate. Vanneaville et al. study used a laparoscopic meso-
varian radiotracer injections in the normal ovaries of 14
patients who were treated for benign ovarian cysts or
were candidate of tubal ligation. Sentinel nodes were
Table 1 Characteristics of the included patients (Continued)
24 45/left/7 × 6 L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: Two hot sentinel nodes
were identified during surgery in the
para-aortic (one) and external iliac (one)
areas. Sentinel nodes were not involved.
No other lymph node involvement.
25 22/right/10 × 11 L Benign serous cyst One/Para-aortic –
26 57/right/8 × 9 L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: The hot sentinel node
was identified during surgery in the
para-aortic area. Sentinel node was not
involved. No other lymph node involvement.
27 43/Bilateral/11 ×
12;10 × 6
L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: The hot sentinel nodes
were identified during surgery in the
para-aortic (two sentinel nodes) and pelvic
areas (right common iliac). None were
involved. No other lymph node involvement.
28 36/right/11 × 10 L Benign serous cyst One/Para-aortic –
29 35/Bilateral/10 ×
10;10 × 7
L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: Two hot (and blue) sentinel
nodes were identified during surgery in the
para-aortic area. One sentinel node was
pathologically involved. No other lymph
node involvement.
30 50/right/7 × 8 L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: The hot (and blue) sentinel
node was identified during surgery in the
pelvic area (external iliac). Sentinel node was
not involved. No other lymph node
involvement.
31 43/Right/10 × 10 L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: The hot (and blue) sentinel
node was identified during surgery in the
pelvic area (external iliac). Sentinel node was not
involved. No other lymph node involvement.
32 36/Right/10 × 12 L Benign mucinous
cystadenoma
One/Para-aortic –
33 35/Bilateral/10 × 8;8 × 8 L Papillary serous
adenocarcinoma
No remaining activity in the
pelvis and abdomen
TAH + BSO + APAL: Two hot (and blue) sentinel
nodes were identified during surgery in the
para-aortic area. One of the sentinel nodes was
involved. One non-sentinel node in the
para-aortic was also involved.
34 45/Left/7 × 7 C Benign serous cyst None –
35 37/Left/8 × 8 C Benign serous cyst None –
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detected 4–6 h post injection by planar lymphoscintigra-
phy. In 12 patients sentinel nodes could be identified (4
para-aortic and 8 pelvic/para-aortic). Isolated para-aortic
drainage was more prominent in the post-menopausal
(75 %) as compared to the pre-menopausal patients
(12.5 %) [18, 20].
An important study published by Kleppe et al. reported
the first experience on sentinel node mapping in ovarian
tumors. They used radiotracer/blue dye injection into the
proper ovarian ligament and the suspensory ligament and
reported 100 % detection rate and sensitivity [17, 21].
Our study showed that intra-operative injection of ra-
diotracer is a feasible method for lymphatic mapping
and sentinel node biopsy in ovarian tumors. Intra-
operative injection of sentinel node mapping materials
has been reported to be very successful for lymphatic
mapping in other solid tumors too; such as lung,
gynecological, and urological tumors [11, 12, 22]. This is
possible due to very rapid movement of the radiotracer
in the lymphatic vessels especially those with small par-
ticle size [23–25]. In the current study we used Tc-99m
Phytate which has a small particle size with rapid lymph-
atic movement as shown in other studies before [26–30].
Negishi et al., Nyberg et al., and Kleppe st al. used
10 min, 10–21 min, and 15 min after injection, respect-
ively. All these three studies had excellent sentinel node
detection rate. We waited for 10 min after injection with
comparable detection rate too. Overall, it seem that 10
to 15 min is an optimal time to wait after mapping ma-
terial injection in ovarian cancers.
Two injection methods were used in our study: sub-
cortical vs. sub-peritoneal. Subcortical injection of the
radiotracer was not successful enough (40 % detection
rate). Finding normal cortex in the tumoral ovaries can
be very hard and carries the risk of tumor puncture and
it seems that sub-cortical injection of the mapping material
is not a viable method for lymphatic mapping in ovarian
cancers. On the other hand injection of the tracer beneath
the peritoneum of the suspensory and utero-ovarian liga-
ments was highly successful for lymphatic mapping (84 %
detection rate). All sentinel node detection failure in this
group occurred in patients with ovarian torsion (3 patients)
which can disrupt the lymphatic flow of the ovaries. Our re-
sults are in accordance with Kleppe et al. report as they also
hadaveryhighdetectionrateusingthesameinjection
method as we used in our study [17, 21].
We used a combination method (blue dye/radiotracer)
in four patients and all four patients had blue para-
aortic sentinel nodes. Adding blue dye to radiotracer
(dual mapping method) has been shown to be an effect-
ive method for decreasing sentinel node detection failure
as well as false negative cases in many tumors [31–33].
However, Kleppe et al. showed that blue dye was suc-
cessful only in 2 patients out of 6 with retro-peritoneal
exploration and ascribed it to the long time between
blue dye injection and exploration [17]. Considering the
possibility of adverse reactions to blue dyes [34, 35], the
added value of blue dye injection should be evaluated in
more detail in the future studies.
Fig. 3 Planar anterior/posterior lymphoscintigraphy images of a patient. Two para-aortic sentinel nodes are marked by arrows. Activity in the liver
is also apparent (black arrows)
Fig. 2 Ablue para-aortic sentinel node could be identified in this
patient intra-operatively (arrow)
Hassanzadeh et al. Journal of Ovarian Research (2016) 9:55 Page 5 of 8
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Imaging of the sentinel nodes using lymphoscintigra-
phy is an important method which is integrated in
lymphatic mapping of the solid tumors [19, 30, 36–39].
We also used lymphoscintigraphy for all patients post-
operatively. For patients with benign pathology; who did
not underwent lymph node dissection, this is the only
method to show the exact location of the sentinel nodes.
For patients with malignant tumors, lymphoscintigraphy
could confirm the complete resection of the sentinel
nodes. Kleppe et al. didn’t use lymphoscintigraphy and
for benign ovarian tumors relative intra-operative count
of the para-aortic or pelvic areas was used as the surro-
gate of the sentinel node detection. This is a limitation
of Kleppe et al. study which we avoided by adding post-
operative lymphoscintigraphy to our study [17, 21]. In
the future studies, application of intra-operative gamma
cameras as well as SPECT/CT methods should be evalu-
ated for sentinel node mapping in ovarian cancers.
The location of sentinel nodes in our study was also in
accordance with the known primary lymphatic drainage
pattern of the ovaries [18]: isolated para-aortic drainage
in 84 %, isolated pelvic drainage in 8 % and combined
pelvic/para-aortic in 8 % of the patients with successful
lymphatic mapping. The variable lymphatic drainage pat-
tern of the ovaries can be problematic in sentinel node
mapping. Intra-operative gamma camera and pre-operative
SPECT/CT can be of particular use in localization of the
ovarian sentinel nodes and future studies should investigate
these flourishing technologies.
Falsenegativerateisanotherimportantindexofthesen-
tinel node mapping studies and should be considered
alongside the detection rate in all sentinel node mapping
feasibility study [40]. In the Kleppe et al. study, only one
patient had involved nodes which were detected by sentinel
node mapping [17]. In our study, three patients had in-
volved lymph nodes and all were correctly identified by
sentinel node biopsy (false negative rate of 0 % which
means 100 % sensitivity). This is promising, however more
studieswithlargersamplesizeisneededtoconfirmthere-
sults of our study. Specificity is not reported in our study
as specificity of sentinel node mapping is always 100 % and
no false positive case is possible. As sentinel node is a part
Table 2 Summary of the studies on lymphatic mapping of the ovaries
First author/year Included patients Mapping material Injection site Main results
Kleppe/2014 21 patients diagnosed with
a pelvic mass suggestive of
a malignant ovarian tumor
Blue dye/
Radiotracer
On the dorsal and ventral side of
the proper ovarian ligament and
the suspensory ligament, close
to the ovary and just underneath
the peritoneum
Al least one sentinel node
could be identified in all
patients (100 % detection
rate). Para-aortic region only
in 67 %, pelvic region only
in 9 %, and in both in 24 %.
No false negative case
Negishi/2004 11 women with endometrial
or fallopian tube tumors
Activated Charcoal Into the unilateral cortex of the ovary Sentinel node could be
identified in all patients:
para-aortic in all patients,
common iliac node in
three, and external iliac in one
Nyberg/2011 16 patients with high-risk uterine
cancer and normal postmenopausal
ovaries
Blue dye/
Radiotracer
Slow injection near the hilum of
one ovary
Sentinel node could be
identified in 15 patients
(93.75 % detection rate).
All were located in the
para-aortic area.
Vanneaville/1991 14 patient who were investigated
by laparoscopy, either for ablation
of a benign ovarian cyst or for
tubal ligation
Radiotracer Injection into the mesovarium
of the normal ovaries during
laparoscopy.
Lymphatic drainage could
be discerned in 12 patients.
Isolated para-aortic sentinel
nodes in 4, combined pelvic/
para-aortic sentinel nodes in 8.
Lymphatic drainage was investigated
by lymphoscintigraphy 4–6h
post-injection.
Isolated para-aortic drainage
was more prominent in the
post-menopausal (75 %) as
compared to the pre-menopausal
patients (12.5 %).
The current study 35 patients with ovarian tumors Radiotracer Sub-cortical in 11 and sub-peritoneal
(ovarian and suspensory ligaments)
in 24
Detectionrateof40%inthe
sub-cortical and 84 % in the
sub-peritoneal group. Sentinel
nodes were identified in 21
patient in the para-aortic area
only and in 4 in the pelvic/
para-aortic area. No false negative
case was identified
Hassanzadeh et al. Journal of Ovarian Research (2016) 9:55 Page 6 of 8
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of the lymphatic basin, pathologically involved sentinel
node invariably means involved lymphatic basin and false
positive case is impossible.
If the results of our study would be corroborated in
the larger multicenter trials, para-aortic and pelvic
lymph node dissection can be omitted in patients with
non-involved sentinel nodes.
The radiation safety of sentinel node mapping has
been addressed before in several studies [41]. Radiation
dose to the patients is very low as systemic absorption of
the tracer is minimal and the injection site is removed
from the body during surgery [42]. Radiation to the sur-
gical and nuclear medicine staff as well as the patholo-
gists is also well below the ICRP threshold limit [43].
Conclusion
Sentinel node mapping using intra-operative injection of
the radiotracer is feasible in ovarian tumors. It seems to
be an accurate method for detection of the patients with
involved lymph nodes. Tracer injection in the utero-
ovarian and suspensory ligaments of the ovary just be-
neath the peritoneum seems to be an efficient method
for lymphatic mapping, however technical aspects of this
method should be explored in larger multicenter studies
in the future.
Acknowledgements
Not applicable
Funding
The current study was funded by a grant from the vice chancellery of
research of Mashhad University of Medical Sciences.
Availability of data and materials
All data supporting the conclusion of our manuscript would be available
upon request from the corresponding author. Public storage of the clinical
data of the patients was not approved by the local ethical committee of our
institute.
Authors’contributions
Study concepts: RS, MH, EH, SK. Study design: MH, EH, ZY, RS. Data acquisition:
EH, LZ, SK. Quality control of data and algorithms: EH, RS, LZ. Data analysis and
interpretation: RS, LZ, ZY. Statistical analysis: RS. Manuscript preparation: RS.
Manuscript editing: All authors. Manuscript review: All authors. All authors read
and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
All patients provided written informed consent before enrollment in the study,
and the study was approved by the Local Ethical Committee of Mashhad
University of Medical Sciences under the approval number of 931331.
Author details
1
Women’s Health Research Center, Mashhad University of Medical Sciences,
Mashhad, Iran.
2
Nuclear Medicine Research Center, Mashhad University of
Medical Sciences, Mashhad, Iran.
Received: 18 April 2016 Accepted: 5 September 2016
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