The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) (Q J Nucl Med)

Publications in this journal

• Article: Radiolabeled chemotactic cytokines: new agents for scintigraphic imaging of infection and inflammation.

  J E M van Eerd, O C Boerman, F H M Corstens, W J G Oyen
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  ABSTRACT: Several radiopharmaceuticals are currently used for diagnosis of inflammatory and infectious diseases in patients. Most inflammatory and infectious processes can be visualized with radiolabeled autologous leukocytes, currently considered to be the most appropriate radiopharmaceutical for this purpose. This agent is very well capable to delineate most inflammatory and infectious foci in a relatively short time after injection. The time-consuming and intricate labeling procedure and the handling of potentially contaminated blood, however cause that there is a great interest in the development of new radiopharmaceuticals comprising the same imaging qualities but without these disadvantages. Besides radiolabeled leukocytes several other radiopharmaceuticals, such as (67)Ga-citrate, radiolabeled anti-granulocyte antibodies and FDG are used to image infection and inflammation. These agents accumulate in infectious and inflammatory lesions in a non-specific manner or have suboptimal diagnostic characteristics. Nowadays, there is a great interest in the development of radiolabeled chemotactic and chemokinetic cytokines that accumulate and are retained in infectious and inflammatory foci by specific interaction with infiltrated inflammatory cells. In this review we describe the specific characteristics of the chemotactic and chemokinetic compounds that are currently studied as potential radiopharmaceutical to visualize infectious and inflammatory foci. The characteristics of a series of cytokines (IL-1, IL-2), chemokines (IL-8, PF-4, MCP-1, NAP-2), complement factors (C5a, C5adR), chemotactic peptides (fMLF) and other chemotactic factors (LTB4) are described. The potentials of these compounds to serve as an imaging agent are discussed.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):246-55.
• Article: Radiolabelling of peptides for diagnosis and therapy of non-oncological diseases.

  J Sosabowsky, L Melendez-Alafort, S Mather
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  ABSTRACT: Radiolabelled peptides have significant potential as radiopharmaceuticals for the diagnosis and therapy of receptor-expressing diseases. Methods have been developed for labelling peptides with a variety of radionuclides having a broad range of chemical and physical properties. These methods include both direct (where the radionuclide is bound directly to one or more atoms of the peptide structure) and indirect techniques in which bifunctional coupling agents are employed. Although most commonly applied to date in the field of oncology, a significant number of applications in non-oncological diseases have also been proposed and these can be expected to expand as the technology progresses. An overview is presented of some peptide-receptor systems in radiopharmaceutical development and the techniques which have been employed to radiolabel these peptides with isotopes of iodine, yttrium, indium, gallium, copper and technetium. While many of the examples employed are derived from cancer related indications, identical radiopharmaceutical chemistry can also be applied to peptides with applications in the fields of immunology, infection and other inflammatory conditions.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):223-37.
• Article: The role of labeled Annexin A5 in imaging of programmed cell death. From animal to clinical imaging.

  B L J H Kietselaer, L Hofstra, E A W Dumont, C P M Reutelingsperger, G A K Heidendal
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  ABSTRACT: Programmed cell death plays a critical role in embryology, homeostasis and disease. However, until recently no non-invasive imaging modality has been able to visualize this process directly. Annexin A5 binds to cells undergoing programmed cell death. When labeling this protein, Annexin A5 becomes a tool for the detection of programmed cell death in vitro and in vivo. Labeled Annexin A5 has enabled our group and others to detect programmed cell death non-invasively in animals and patients. This review will highlight the development of this imaging modality in cellular and animal models. Furthermore, we will discuss Annexin A5 imaging in human disease. We will focus on the clinical applications and their relevance, limitations and future perspectives of non-invasive imaging of programmed cell death using labeled Annexin A5.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):349-61.
• Article: Radiolabelled peptides and low molecular weight proteins in metabolic diseases.

  C Aprile
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  ABSTRACT: During the last decade there has been a tremendous effort to develop labelled peptides for diagnosis and therapy. The main goal has been to develop tumor imaging/therapeutic agents, as well as peptides directed to the study of thrombosis and infection. Relatively few efforts have been made to develop peptides directed to the study of metabolic diseases. Ideally, a peptide suitable for the study of metabolism should be constructed keeping in mind the following characteristics: a) preserved affinity constant, b) preserved or improved specificity for its binding site, c) increased biological half-life in comparison with the parent peptide, d) labelling with a g or positron emitter whose physical half-life fits with the biological half-life, e) strong binding of the nuclide to the molecule so that it cannot be released after internalization. In this paper some of the peptides or low molecular weight proteins along with some analogues which have been employed in experimental studies and in humans are reviewed, with major emphasis on amyloid seekers, insulin and leptin. Many of these radiopharmaceuticals have been labelled with iodine isotopes, however their in vivo application suffer of severe limitations due to rapid release of iodine after internalization. On the other hand, new perspectives are opened by new radiofluorination techniques, which offer the unique advantage to quantify organ uptake and kinetics, parameters which are of paramount importance in metabolic studies.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):321-36.
• Article: Non-oncologic applications of radiolabeled peptides in nuclear medicine.

  L C Knight
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  ABSTRACT: Radiolabeled peptides have been investigated for diagnostic imaging in a variety of non-oncologic diseases. For imaging thromboembolic disease, peptides which bind to various components of thrombi have been tested. For targeting the fibrin component of thrombi, peptide analogues of fibrin or fragments of fibronectin which have a distinct binding domain for fibrin have been studied. For targeting activated platelets within thrombi, linear and cyclic peptide antagonists of the glycoprotein IIb/IIIa receptor on platelets have been studied, as well as naturally occurring antagonists of this receptor which are found in venoms. Analogues of laminin and thrombospondin which bind to other receptors on platelets have also been tested. There is an approach which uses a peptide to target thrombin which is sequestered within a fibrin clot. Another area of investigation has been to develop an improved radiopharmaceutical for imaging sites of infection and/or inflammation. Peptides which would bind to leukocytes in vivo, such as antagonists to the tuftsin receptor, chemotactic peptides, interleukin-8, or a platelet factor 4 analogue, have been radiolabeled for this purpose. These agents would enable imaging of both infection and inflammation. Development of a radiopharmaceutical for specifically imaging infection has focused on antimicrobial peptides such as human neutrophil defensin, ubiquicidin, human lactoferrin and alafosfalin, which are expected to bind selectively to microorganisms and not to leukocytes. Radiolabeled peptides are also being explored as agents for assessing unstable atherosclerotic plaque (endothelin), amyloid deposits (amyloid beta peptides), and the consequences of diabetes mellitus (human C-peptide).
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):279-91.
• Article: "Pathophysiologic mapping" of venous thromboembolism: opportunities for radiolabeled peptides.

  M P Bernarducci
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  ABSTRACT: The serious clinical and economic impact of venous thromboembolic (VTE) disease is undisputed. What concerns practitioners and researchers alike is the seeming inability to truly mitigate the ramifications of VTE. Ironically, the current approaches to the diagnostic evaluation of suspected VTE patients tends to favor the application of anatomic modalities, which by virtue of their principles of detection, seemingly ignore the extensive knowledge base of VTE pathophysiology and natural history. In other words, are we seeking the appropriate types of information in patients with suspected VTE? Research in nuclear medicine techniques for detecting VTE began approximately 25 years ago. Recently, the emergence of the radiolabeled peptides as a clinically applicable technology platform has encouraged a different way of evaluating VTE. Many radiolabeled peptide candidates are undergoing preclinical and clinical research. Currently, only one, (99m)Tc-apcitide (AcuTect), has been approved (since 1998) for clinical use, specifically in the United States. Its availability this time has fueled ongoing clinical research to further elucidate the benefits of this unique peptide technology. Consequently, significant insight has been gained from large prospective clinical trials. Furthermore, this insight has kindled increasing interest in (99m)Tc-apcitide and potential new entrants into this special "diagnostic class". Unlike the more popular modalities, radiolabeled peptides circumvent many of the clinical and anatomic challenges to objectively and accurately diagnosing VTE. The importance of an objective and accurate diagnosis is understood, because it is paramount to a cost-effective treatment strategy. In addition to describing the current activities concerning the development for and use of radiolabeled peptides for clinical practice, this manuscript is intended to promulgate a thought-provoking argument for changing our current approach to the diagnostic evaluation of VTE. Despite technological and medical advances, we continue to debate controversial issues in VTE, which seemingly and arguably disproportionately, focus on treatment (i.e., who?, when?, how much? and for how long?). Should we not adopt a more robust approach to VTE problem-solving, which would logically start with the diagnosis? Perhaps the validated and perceived advantages of the radiolabeled peptides are all the rationale we need to advance beyond the status quo? Only time and continued research will tell.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):292-320.
• Article: The role of octreotide scintigraphy in rheumatoid arthritis and sarcoidosis.

  V A S H Dalm, P M van Hagen, E P Krenning
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  ABSTRACT: Somatostatin receptors are widely expressed on cells and tissues throughout the human body. Apart from their expression in the physiological target organs of the peptide, somatostatin receptors are also expressed in various tumours. The expression of somatostatin receptors on neuroendocrine tumours led to the development of somatostatin receptor scintigraphy using [(111)In-DTPA-D-Phe(1)]-octreotide ((111)In-pentetreotide) in order to visualize somatostatin receptor positive tumours and their metastases in vivo. Previous studies reported the expression of somatostatin receptors in both normal and pathological cells and tissues of the human immune system as well. Somatostatin receptors have been demonstrated in Hodgkin's and non-Hodgkin's lymphomas and sst scintigraphy has shown to be a useful tool in diagnosis and staging of these diseases. Moreover, sst expression has also been detected in granulomateus diseases, like sarcoidosis and auto-immune diseases, like rheumatoid arthritis. In this paper we discuss the (possible) role of somatostatin receptor scintigraphy in diagnosis, staging or follow-up of patients suffering from sarcoidosis and rheumatoid arthritis.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):270-8.
• Article: Imaging cell death in vivo.

  F Blankenberg, C Mari, H W Strauss
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  ABSTRACT: A technique to image programmed cell death would be useful both in clinical care and in drug development. The most widely studied agent for the in vivo study of apoptosis is radiolabeled annexin V, an endogenous protein labeled with technectium-99m, now undergoing clinical trials in both Europe and the United States. While annexin V has been studied extensively in humans the precise mechanism(s) of uptake this agent in vivo is unclear and needs further study. Other agents are also under development, including radiolabeled forms of Z-VAD.fmk, a potent inhibitor of the enzymatic cascade intimately associated with apoptosis. In addition other technologies, such as diffusion weighted magnetic resonance imaging and magnetic resonance imaging with contrast agents, such as small paramagnetic iron oxide particles coated with peptides have also been advocated as methods to monitor apoptotic cell death. The potential applications of imaging apoptosis as a marker of early response to therapy in cancer, acute cerebral and myocardial ischemic injury and infarction, immune mediated inflammatory disease and transplant rejection are reviewed.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):337-48.
• Article: The developing role of peptide radiopharmaceuticals in the study of chronic inflammation: new techniques for novel therapeutic options.

  M Chianelli, M G Parisella, C D'Alessandria, F Corsetti, F Scopinaro, A Signore
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  ABSTRACT: Chronic inflammatory diseases usually lead to fibrosis of the target organ and consequent hypo function. They are often relapsing, invalidating and require life-long treatment. In this class of patients it is very important to try and achieve specific immune suppression to extinguish the immune process with the aim of preventing the disease, preventing or delaying complications and avoiding disease relapse, often requiring surgical intervention. It is important that, while attempting to improve the quality of life of these patients by means of anti-inflammatory drugs, side effects are reduced to a minimum via the use of specific immune therapies that block as selectively as possible the pathologic mechanism responsible for the disease. New therapeutic options are being developed for specific targeted therapies. Several trials are being performed to assess the efficacy and safety of this approach. All of them, however, rely on the clinical assessment of the patients to evaluate the effect of treatment. It would be important to use an objective and reliable method to highlight directly the immune process underlying the individual disease. This manuscript reviews the radiopharmaceuticals available or recently developed for imaging chronic inflammatory diseases and their use for therapy decision making and follow-up.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 01/2004; 47(4):256-69.
• Article: Radiotracer-based strategies to image angiogenesis.

  R H Haubner, H J Wester, W A Weber, M Schwaiger
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  ABSTRACT: Tumour-induced angiogenesis plays an important role in tumour progression. Great efforts are made to develop therapeutic strategies to interfere with this process resulting in the starvation of the tumour. However, strategies to monitor conventional therapies seems to be inappropriate to control these approaches. Thus, there is a keen interest in developing methods supplying information about the corresponding therapeutical effects. Several radiotracer-based approaches focused on different targets in the angiogenic process are currently investigated. One class of tracers is based on matrix metalloproteinases inhibitors. These compounds show promising results in in vitro assays. However, initial data from in vivo studies using murine tumour models could not confirm successful non-invasive monitoring of MMP activity yet. Another strategy uses a radiolabelled single chain fragment against the ED-B domain of fibronectin, an extracellular matrix protein. Promising results demonstrated selective accumulation of the tracer in the tumour vasculature of a murine tumour model. Most of the studies are concentrated on the development of radiolabelled antagonists of the integrin alpha(v)beta(3). This heterodimeric transmembrane glycoprotein is involved in the migration of activated endothelial cells during formation of new vessels. Different compounds have been labelled with (18F), (111)In, (99m)Tc, (90)Y and several iodine isotopes. In in vitro assays most of them revealed high alpha(v)beta(3) affinity and selectivity. Moreover, in different murine tumour models successful non-invasive determination of alpha(v)beta(3) expression has been shown. Some of these approaches indicate that tumour-induced angiogenesis can be monitored in animal studies. Nevertheless, translation of these approaches into clinical settings allowing visualisation of tumour-induced angiogenesis in patients needs still to be demonstrated.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 10/2003; 47(3):189-99.
• Article: Imaging matrix metalloproteinase expression in tumors.

  W P Li, C J Anderson
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  ABSTRACT: metastatic Matrix metalloproteinases (MMPs) are zinc-dependent secreted or transmembrane enzymes constituting a family of over 21 proteolytic members that are capable of selectively digesting a wide spectrum of both extracellular matrix (ECM) and nonmatrix proteins. MMPs play a critical role in tumor growth, angiogenesis, and metastatic processes. MMP inhibitors (MMPIs) have been extensively investigated as anti-tumor drugs, although the clinical trials thus far have been disappointing. In order to better understand the role of MMPs in cancer growth and metastasis, as well as improve the therapeutic efficacy of MMPIs, there is a need to develop new procedures to assess and/or monitor MMP activity in vivo. In addition to determining whether MMPs are present in tumors, it would be desirable to have an imaging agent that better probes other processes associated with MMP overproduction, including angiogenesis and the establishment of the growth of metastatic lesions in distant organ sites. In this paper we review the studies relating to the recent development of in vivo imaging of MMP expression. One of the purposes of this review is to discuss the current status of imaging MMP expression, which includes the types of tracers being developed and the types of imaging modalities available. Although imaging MMP expression is a relatively new area of research, the progress thus far is highly promising.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 10/2003; 47(3):201-8.
• Article: Angiogenic and angiostatic factors in the molecular control of angiogenesis.

  J H W Distler, A Hirth, M Kurowska-Stolarska, R E Gay, S Gay, O Distler
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  ABSTRACT: The vascular system that ensures an adequate blood flow is required to provide the cells with sufficient supply of nutrients and oxygen. Two different mechanisms of the formation of new vessels can be distinguished: vasculogenesis, the formation of the first primitive vascular plexus de novo and angiogenesis, the formation of new vessels from preexisting ones. Both processes are regulated by a delicate balance of pro- and anti-angiogenic factors. Physiologically, angiostatic mediators outweigh the angiogenic molecules and angiogenesis does not occur. Under certain conditions such as tumor formation or wound healing, the positive regulators of angiogenesis predominate and the endothelium becomes activated. Angiogenesis is initiated by vasodilatation and an increased permeability. After destabilization of the vessel wall, endothelial cells proliferate, migrate and form a tube, which is finally stabilized by pericytes and smooth muscle cells. Numerous soluble growth factors and inhibitors, cytokines and proteases as well as extracellular matrix proteins and adhesion molecules strictly control this multi-step process. The properties and interactions of angiogenic molecules such as VEGFs, FGFs, angiopoietins, PDGF, angiogenin, angiotropin, HGF, CXC chemokines with ELR motif, PECAM-1, integrins and VE-cadherin as well as angiostatic key players such as angiostatin, endostatin, thrombospondin, CXC chemokines without ELR motif, PEDF are discussed in this review with respect to their molecular impact on angiogenesis.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 10/2003; 47(3):149-61.
• Article: Imaging the effects of anti-angiogenic treatments.

  A L Vāvere, J S Lewis
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  ABSTRACT: It is clear that various imaging modalities have given keen insight into the molecular mechanisms involved in anti-angiogenic treatments. A key to the advancement of anti-angiogenic therapy is not only the discovery of new drugs and treatments, but the analysis of the specific modes of action of these compounds in order to produce the next generation with greater effectiveness. While existing clinical methods incorporate the analysis of serum and urine to measure angiogenic factors, an imaging technique monitoring the effectiveness of anti-angiogenic therapy would be a convenient, noninvasive, cost effective technique to aid in treatment planning and disease management.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 10/2003; 47(3):163-70.
• Article: Radiopharmaceuticals for targeting the angiogenesis marker alpha(v)beta(3).

  P McQuade, L C KnIght
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  ABSTRACT: A common feature of solid tumors is the formation of new blood vessels (angiogenesis) within the tumor. A receptor called alpha(v)beta(3) is found on endothelial cells lining newly growing blood vessels at a higher density than on mature blood vessels. This receptor may provide a target for radioligands to permit imaging of a wide variety of solid tumors. The radioligands may range from macromolecules such as native ligands or monoclonal antibodies, to small proteins to very small peptides. The differing characteristics of these bio-molecules have an affect on target delivery and clearance time.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 10/2003; 47(3):209-20.
• Article: CT imaging of angiogenesis.

  T-Y Lee, T G Purdie, E Stewart
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  ABSTRACT: Tumor angiogenesis has significant implications in the diagnosis and treatment of various solid tumors. With the advent of fast, multi-slice CT scanners, CT imaging techniques capable of qualitative and quantitative analysis of tumor angiogenesis have been the subject of extensive investigation in the past 2 decades. The fundamental bases for CT imaging of angiogenesis are both the transport by blood flow of intravenously administered iodinated contrast material to tissue and the exchange by diffusion of these contrast molecules between the intravascular space and the extravascular interstitial space. With current fast CT scanners both tissue and vascular enhancement can be measured and traced over time at small time intervals to allow detailed modeling of the distribution of contrast agent in tissue. Both compartmental and distributed parameter models for contrast transport and exchange have been developed to quantify from the CT data the following angiogenesis related parameters: tissue blood flow, blood volume, mean transit time, contrast arrival time, capillary permeability surface area product and hepatic arterial fraction in case of the liver. This review addresses the following aspects of CT imaging of angiogenesis: 1) basic concepts related to the understanding of both compartmental and distributed parameter models; 2) comparison between both types of models; 3) practical issues with respect to the measurement of the arterial input function, which is required for the solution of both types of models; and, 4) illustration of the application of a distributed parameter model, the Johnson and Wilson model, in a number of experimental studies.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 10/2003; 47(3):171-87.
• Article: Radioimmuno targetting (99m)technetium labeled anti-epidermal growth factor receptor monoclonal antibodies in experimental tumor models.

  A Meenakshi, V Ganesh, R Suresh Kumar, N Siva Kumar
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  ABSTRACT: Monoclonal antibodies (MAb) directed at the extra cellular domain (ECD) of epidermal growth factor receptor (EGFR) offer a promising strategy for diagnosis and therapy of cancers that over-express EGFR. Radiolabelled MAbs against cell surface antigens have improved in vivo tumor diagnosis and treatment. EGFR over-expression has been reported in a wide range of carcinomas especially of the head and neck, breast, etc., and is associated with poor prognosis and resistance to therapy. CIBCNSH3 is a murine MAb generated to the ECD of EGFR in our laboratory and has been extensively characterized and has proven antitumor activity. The tumor targeting potential of (99m)Tc labelled CIBCNSH3 in an experimental tumor model is discussed in this paper. A431, an epidermoid carcinoma cell line with overexpression of EGFR, SUDHLH, a lymphoma cell line was used to induce xenografts in inbred adult female BALB/C mice and used for the study. A reduction mediated method of (99m)Tc labelling was adopted to label the MAb. Scintiscan pictures were taken at different time intervals after i.v. administration of the (99m)Tc labelled MAb using a gamma camera and results were correlated with those of biodistribution studies. Immunoscan pictures taken at different time periods showed high uptake of the radioimmunoconjugate by the tumor providing clear tumor images and no uptake in control animals with lymphoma xenografts. Results of scan pictures correlated well with the biodistribution studies. The radioimmunoconjugate (99m)Tc-CIBCNSH3 appears to be a promising tool in identifying any early recurrence and micro-metastasis of lesions that overexpress EGFR.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 07/2003; 47(2):139-44.
• Article: Importance of radio-guided minimally invasive parathyroidectomy using hand-held gamma probe and low (99m)Tc-MIBI dose. Technical considerations and long-term clinical results.

  D Rubello, D Casara, S Giannini, A Piotto, E De Carlo, P C Muzzio, M R Pelizzo
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  ABSTRACT: (99m)Tc-MIBI radio-guided surgery results, obtained in a group of 141 patients with primary hyperparathyroidism (HPT), are reported. All patients were preoperatively evaluated by a single day protocol based on double-tracer parathyroid scintigraphy and neck ultrasound, and then operated by the same surgical team. In 102 patients (72.3%) with a high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, a minimally invasive radio-guided surgery was planned. In the other 39 patients (27.7%) with scan/ultrasound evidence of multi-glandular disease (n=8) or concomitant nodular goiter (n=31), the intraoperative gamma probe was used during a standard bilateral neck exploration. Intraoperative quick parathyroid hormone (PTH) levels were routinely measured. The minimally invasive radio-guided surgery technique we developed, consisted of: a) injection of a low 37 MBq (99m)Tc-MIBI dose in the operative theatre during anaesthesia induction, b) patient's neck scan with a hand-held gamma probe just before the surgical cut to localize the cutaneous projection of the parathyroid adenoma, c) intraoperative probe detection of the parathyroid adenoma and its removal through a small 2-2.5 cm skin incision. Minimally invasive radio-guided surgery was successfully performed in 99/102 patients (97.0%). The gamma probe was particularly useful in patients with an ectopic parathyroid adenoma in the upper mediastinum (n=11) or to the carotid bifurcation (n=1) or located deep in the neck (n=8). Minimally invasive radio-guided surgery was also obtained in 18/23 patients who had previously undergone thyroid/parathyroid surgery. The mean operative time for minimally invasive radio-guided surgery was 38 min. No major surgical complication was recorded. Conversion to bilateral neck exploration was required in only 3 cases because of intra-operative diagnosis of parathyroid carcinoma (n=2), and persistence of elevated quick PTH levels after removal of the preoperatively visualized parathyroid adenoma (n=1). Among patients treated by standard bilateral neck exploration, the gamma probe was useful in localizing a thymical enlarged parathyroid gland in 1 patient with multi-glandular disease, a parathyroid adenoma located deep in the neck in 4 patients with concomitant nodular goiter and an ectopic parathyroid adenoma to the carotid bifurcation in another. However, in some other patients with a parathyroid adenoma located near to the thyroid, it was difficult to intraoperatively distinguish the parathyroid adenoma from a MIBI avid thyroid nodule. It can be concluded that: (a) in primary HPT patients with high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, the gamma probe appears to be an effective, rapid and safe technique to perform minimally invasive radio-guided surgery; b) a (99m)Tc-MIBI dose as low as 37 MBq appears to be adequate to successfully perform radio-guided surgery; c) the measurement of quick PTH is recommended during minimally invasive radio-guided surgery; d) minimally invasive radio-guided surgery can be performed also in HPT patients with previous parathyroid/thyroid surgery thus limiting surgical trauma; e) with the possible exception of parathyroid adenoma located in ectopic sites or deep in the neck, the gamma probe technique does not seem recommendable in HPT patients with concomitant nodular goiter.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 07/2003; 47(2):129-38.
• Article: Paraneoplastic syndromes: detection of malignant tumors using [(18)F]FDG-PET.

  U Berner, C Menzel, D Rinne, S Kriener, N Hamscho, N Döbert, M Diehl, R Kaufmann, F Grünwald
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  ABSTRACT: Paraneoplastic syndromes (PS) comprise a variety of clinical symptoms and diseases associated with underlying malignancy. Differentiation towards benign autoimmune diseases is necessary due to different therapeutic options. This diagnostic challenge includes cost- and time-consuming methods and is not successful in many cases. The aim of this study was the evaluation of [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) for detecting or ruling out malignancy in these patients. In this retrospective work-up a total of 30 patients with suspected PS (m:f = 17:13, mean age 55, range 22-76 years) were examined with [(18)F]FDG-PET between 1996 and 2001. Diagnoses were erythrodermia, cerebellar degeneration, dermatomyositis, polyneuropathia and others. PET scans were compared to histopathological (n=14), radiological and follow up data (mean follow up 3.6 years, range 1-6 years). In 7 out of 30 patients (23%) an underlying malignancy was detected. Six out of 7 malignant neoplasms showed a distinctly increased glucose consumption. One benign neoplasm caused increased tracer uptake, another PET positive patient refused biopsy and showed no growth of a malignant tumour during clinical follow up of 28 months. The remaining 21 patients without suspicious glucose consumption did not demonstrate a malignancy in other diagnostic modalities or during subsequent clinical follow-up. [(18)F]FDG-PET seems to be a useful tool in the diagnostic work-up of patients with suspected paraneoplastic syndrome.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 07/2003; 47(2):85-9.
• Article: Advanced ovarian carcinoma: usefulness of [(18)F]FDG-PET in combination with CT for lesion detection after primary treatment.

  M Picchio, S Sironi, C Messa, G Mangili, C Landoni, L Gianolli, B Zangheri, R Viganò, G Aletti, P De Marzi, F De Cobelli, A Del Maschio, A Ferrari, F Fazio
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  ABSTRACT: To determine the additional value of [(18)F]FDG-PET in combination with computed tomography (CT) over CT used alone, for evaluating ovarian cancer patients after primary treatment. Twenty-five women (mean age: 53.6 years) had primary debulking surgery followed by chemotherapy for histologically proven ovarian carcinoma. At initial diagnosis, the tumor types were papillary serous adenocarcinoma (n=20), endometroid carcinoma (n=3), mixed mullerian tumor (n=1), and granulosa cell tumor (n=1). All patients underwent [(18)F]FDG-PET and contrast enhanced CT examinations, within 30 days of the completion of chemotherapic treatment. [(18)F]FDG-PET images were interpreted with the knowledge of CT findings (PET+CT); conversely, CT images were evaluated with no knowledge of the [(18)F]FDG-PET results. Within 7 day of imaging studies, 2(nd)-look laparoscopy (n=7) or laparotomy (n=18) was performed for histological confirmation. In all cases, imaging findings were then correlated with results of histopathologic examination. Of the 23 neoplastic viable lesions, all histologically confirmed, 16 could be detected by CT alone and 19 by PET+CT. An inflammatory lymph-node was misdiagnosed as viable tumor with both PET+CT and CT alone; an area of scar tissue in the presacral region was also misinterpreted as malignant tissue with CT alone. Overall lesion-based sensitivity, specificity and accuracy in assessing focal areas of residual tumor were as follows: 69.56%, 83.33%, 74.28% for CT, and 82.60%, 91.67%, 85.71% for PET+CT. The negative predictive value of PET+CT was markedly higher (73.33%), compared to that of CT alone (58.82%). PET used in combination with CT allows to accurately assess tumor response. A major advantage of PET+CT over CT alone is in excluding the presence of residual viable lesions after treatment.
  The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 07/2003; 47(2):77-84.