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Radioimmunotherapy has demonstrated efficacy with acceptable toxicity leading to approval in non-Hodgkin's lymphoma, but has been slower to develop for the treatment of advanced solid tumors. Prostate cancer represents a good candidate for radioimmunotherapy based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen in prostate-specific membrane antigen. Four phase I and II trials utilizing 177Lu-or 90Y-J591 have been reported. Long-term toxicity and chemotherapy administration was analyzed. As expected, the only serious toxicity observed was myelosuppression. Grade 4 thrombocytopenia occurred in 33.3% without significant hemorrhage and grade 4 neutropenia occurred in 17.3% with 0.07% febrile neutropenia. Nearly all subjects (97.3%) recovered to grade 0 or 1 platelets and all had complete neutrophil recovery. The majority (81.3%) received chemotherapy at any time, with 61.3% receiving chemotherapy following radioimmunotherapy. Ten subjects underwent bone marrow biopsies at some point in their disease course following radioimmunotherapy for low counts; all had diffuse prostate cancer infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of radioimmunotherapy for men with metastatic castration-resistant prostate cancer. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following radioimmunotherapy. [ABSTRACT FROM AUTHOR]

Pigmented villonodular synovitis (PVNS) is an uncommon musculoskeletal tumor that is typically benign and often diagnosed radiologically by magnetic resonance imaging (MRI). Fluorodeoxyglucose (FDG)-uptake positron emission tomography (PET) is an imaging tool primarily used in oncology to evaluate malignancy. FDG measures metabolic activity with standardized uptake value (SUV). A high SUV is suggestive of malignancy. We report a case of PVNS detected incidentally by FDG-PET as an extracapsular mass adherent to vastus medialis tendon with a high SUV of 15.1. Given the patient's history of cancer and the high SUV, the lesion was initially considered a malignancy. The objective of this case report is to illustrate that even a high-SUV mass detected with PET imaging does not necessarily indicate malignancy, and thus a benign lesion can also demonstrate such elevated signal. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS: Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2-4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS: Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute's Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. CONCLUSIONS: Fractionated radioimmunotherapy with 90Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Ablation of residual thyroid tissue after total or near-total thyroidectomy is widely accepted by many practitioners and endorsed by relevant professional societies in the United States and the international community for patients with defined risk factors, including age greater than 45 years, large tumors; tumors with undesirable histopathology; lymph node involvement; positive surgical margins; gross and possibly microscopic extrathyroidal extension; and, of course, evidence or suspicion of distal metastases, including mediastinal lymphadenopathy, pulmonary or osseous metastases or involvement of other organs. (131)I therapy doses of 3.7-5.5 GBq (100-150 mCi) should be used, and additional activity should be used in the event there are additional findings on pretreatment whole-body scans. Depending upon the patient's age, general medical condition, and renal function, nuclear medicine practitioners should be prepared to perform whole body (blood or bone marrow) dosimetry in the event doses >5.5 GBq (150 mCi) are being considered to assure patient safety. Still unresolved is the role of (131)I ablation in the so-called "low risk" patient--particularly in a patient who has undergone a near-total thyroidectomy in the hands of a skilled surgeon. If an ablative dose is to be administered, 0.9-1.8 MBq (25-50 mCi) appears to be sufficient to eliminate most if not all thyroid tissue. The problem is defining the "low-risk" patient. After review of the extensive literature on this subject, it appears that the thoughtful and informed practitioner must make a patient specific decision in this setting on the basis of his/her experience and review of the details in each case and continue to review the evidence on this subject as it becomes available. [ABSTRACT FROM AUTHOR]

Ablation of residual thyroid tissue after total or near-total thyroidectomy is widely accepted by many practitioners and endorsed by relevant professional societies in the United States and the international community for patients with defined risk factors, including age greater than 45 years, large tumors; tumors with undesirable histopathology; lymph node involvement; positive surgical margins; gross and possibly microscopic extrathyroidal extension; and, of course, evidence or suspicion of distal metastases, including mediastinal lymphadenopathy, pulmonary or osseous metastases or involvement of other organs. 131I therapy doses of 3.7-5.5 GBq (100-150 mCi) should be used, and additional activity should be used in the event there are additional findings on pretreatment whole-body scans. Depending upon the patient''s age, general medical condition, and renal function, nuclear medicine practitioners should be prepared to perform whole body (blood or bone marrow) dosimetry in the event doses >5.5 GBq (150 mCi) are being considered to assure patient safety. Still unresolved is the role of 131I ablation in the so-called “low risk” patient—particularly in a patient who has undergone a near-total thyroidectomy in the hands of a skilled surgeon. If an ablative dose is to be administered, 0.9-1.8 MBq (25-50 mCi) appears to be sufficient to eliminate most if not all thyroid tissue. The problem is defining the “low-risk” patient. After review of the extensive literature on this subject, it appears that the thoughtful and informed practitioner must make a patient specific decision in this setting on the basis of his/her experience and review of the details in each case and continue to review the evidence on this subject as it becomes available. [Copyright &y& Elsevier]

Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, 18F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET/CT imaging of prostate cancer. Among these, choline labeled with 18F or 11C, 11C-acetate, and 18F-fluoride has demonstrated promising results, and other new radiopharmaceuticals are under development and evaluation in preclinical and clinical studies. Large prospective clinical PET/CT trials are needed to establish the role of PET/CT in prostate cancer patients. Because there are only limited available therapeutic options for patients with advanced metastatic prostate cancer, there is an urgent need for the development of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies) and small volume disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate cancer. [Copyright &y& Elsevier]

Radioimmunotherapy is a form of targeted radionuclide therapy that uses a monoclonal antibody to deliver localized radiation. It is most appropriate for treatment of multiple tumor sites that cannot be readily excised surgically or irradiated using external beam radiation or brachytherapy. At present, 2 products, Bexxar (131I-tositumomab and unlabeled tositumomab, GlaxoSmithKline, Triangle Park, NC) and Zevalin (90Y-ibritumomab tiuxetan and unlabeled rituximab, Spectrum Pharmaceuticals, Irvine, CA and Cell Therapeutics, Seattle, WA) are approved for treatment of non-Hodgkin''s lymphoma in certain clinical situations in the United States and Canada. Zevalin is available also in Europe, and there are plans to make both agents more widely available. The therapeutic dose to be used depends upon a number of patient-specific variables. Both regimen achieve a complete response or partial response in approximately 3 of 4 patients, with a duration of remission lasting many years in some cases. This article reviews the basis for dose selection, the nuclear medicine procedures involved, the results obtained to date, and issues related to patient and staff safety. [Copyright &y& Elsevier]

Summary: We have determined the systemic biodistribution of the hormone leptin by PET imaging. PET imaging using 18F- and 68Ga-labeled leptin revealed that, in mouse, the hormone was rapidly taken up by megalin (gp330/LRP2), a multiligand endocytic receptor localized in renal tubules. In addition, in rhesus monkeys, 15% of labeled leptin localized to red bone marrow, which was consistent with hormone uptake in rodent tissues. These data confirm a megalin-dependent mechanism for renal uptake in vivo. The significant binding to immune cells and blood cell precursors in bone marrow is also consistent with prior evidence showing that leptin modulates immune function. These experiments set the stage for similar studies in humans to assess the extent to which alterations of leptin''s biodistribution might contribute to obesity; they also provide a general chemical strategy for 18F labeling of proteins for PET imaging of other polypeptide hormones. [Copyright &y& Elsevier]

Gallium-67 (67Ga)-citrate was initially introduced as a tumor imaging agent in the early 1970s, but it was soon recognized that it was useful in the identification of both acute and chronic inflammation. Because of its physical characteristics (multiple γ photons energy; long half life) and binding to the plasma protein transferrin (resulting in relatively high background and therefore reduced lesion-to-background contrast), it was less than ideal as an imaging agent. Several years later, it became possible to radiolabel leukocytes, which had the advantage of greater specificity for acute infections characterized by a granulocytic response, but had the disadvantage of requiring the removal of blood and isolation of the leukocyte component. Several radiolabeled antibody preparations and a radiolabeled antibacterial agent have been introduced and evaluated, but none of these have been used widely. Most recently, it has been recognized that the use of 18F-fluorodeoxyglucose can be used to identify infection/inflammation, probably based on the focal increase in anaerobic glucose metabolism associated with the cellular response. In this work, we review the features of each of these agents and discuss the issues involved in their use as radiopharmaceuticals for the identification of inflammation and/or infection. [Copyright &y& Elsevier]