Meta-iodobenzylguanidine (MIBG) labeled with 123 I or 131 I has been widely used for the diagnosis and radiotherapy of norepinephrine transporter (NET)-expressing tumors. However, 123 I/ 131 I-MIBG has limitations for detecting small lesions because of its lower spatial resolution than PET tracers. In this study, meta-bromobenzylguanidine (MBBG) labeled with 76 Br (half-life, 16.1 h), an attractive positron emitter, was prepared and evaluated as a potential PET tracer for imaging NETexpressing tumors. Methods: 76 Br-MBBG was prepared by a halogen-exchange reaction between the 76 Br and iodine of nonradioactive MIBG. The stability of MBBG was evaluated in vitro and in vivo by high-performance liquid chromatography analysis. Cellular uptake studies with or without NET inhibitors were performed in NET-positive PC-12 cell lines. Biodistribution studies were performed in PC-12 tumor-bearing nude mice by administration of a mixed solution of MBBG, MIBG, and 18 F-FDG. The tumor was imaged using 76 Br-MBBG and 18 F-FDG with a small-animal PET scanner. Results: MBBG was stable in vitro, but some time-dependent dehalogenation was observed after administration in mice. MBBG showed high uptake in PC-12 tumor cells that was significantly decreased by the addition of NET inhibitors. In biodistribution studies, MBBG showed high tumor accumulation (32.0 6 18.6 percentage injected dose per gram at 3 h after administration), and the tumor-to-blood ratio reached as high as 54.4 6 31.9 at 3 h after administration. The tumor uptake of MBBG correlated well with that of MIBG (r 5 0.997) but not with that of 18 F-FDG. 76 Br-MBBG PET showed a clear image of the transplanted tumor, with high sensitivity, which was different from the lesion shown by 18 F-FDG PET. Conclusion: 76 Br-MBBG showed high tumor accumulation, which correlated well with that of MIBG, and provided a clear PET image. These results indicated that 76 Br-MBBG would be a potential PET tracer for imaging NETexpressing neuroendocrine tumors and could provide useful information for determining the indications for 131 I-MIBG therapy.

PurposeTherapeutic options for patients with malignant pheochromocytoma are currently limited, and therefore new treatment approaches are being sought. Targeted radionuclide therapy provides tumor-specific systemic treatments. The β-emitting radiopharmaceutical meta-131I-iodo-benzylguanidine (131I-MIBG) provides limited survival benefits and has adverse effects. A new generation of radionuclides for therapy using α-particles including meta-211At-astato-benzylguanidine (211At-MABG) are expected to have strong therapeutic effects with minimal side effects. However, this possibility has not been evaluated in an animal model of pheochromocytoma. We aimed to evaluate the therapeutic effects of the α-emitter 211At-MABG in a pheochromocytoma model.MethodsWe evaluated tumor volume-reducing effects of 211At-MABG using rat pheochromocytoma cell line PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections of 211At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq; five mice per group). Tumor volumes were evaluated for 8 weeks after 211At-MABG administration. The control group of ten mice received phosphate-buffered saline.ResultsThe 211At-MABG-treated mice showed significantly lower relative tumor growth during the first 38 days than the control mice. The relative tumor volumes on day 21 were 509.2% ± 169.1% in the control mice and 9.6% ± 5.5% in the mice receiving 0.56 MBq (p < 0.01). In addition, the mice treated with 0.28, 0.56 and 1.11 MBq of 211At-MABG showed only a temporary weight reduction, with recovery in weight by day 10.Conclusion211At-MABG exhibited a strong tumor volume-reducing effect in a mouse model of pheochromocytoma without weight reduction. Therefore, 211At-MABG might be an effective therapeutic agent for the treatment of malignant pheochromocytoma.Electronic supplementary materialThe online version of this article (10.1007/s00259-017-3919-6) contains supplementary material, which is available to authorized users.

Summary:To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early-and/or late-onset HC (early ¼ 29, late ¼ 48, both ¼ 4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (P ¼ 0.0079, odds ratioCI ¼ 2.055-9.292), antithymocyte globulin (P ¼ 0.0009, OD ¼ 3.368, 95% CI ¼ 1.642-6.911), nonradiation (P ¼ 0.0163, OD ¼ 2.564, 95% CI ¼ 0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (P ¼ 0.0001, OD ¼ 7.519, 95% CI ¼ 2.847-19.858), and bladder irrigation (P ¼ 0.0001, OD ¼ 4.950, 95% CI ¼ 2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (Po0.001) than Mesna alone (P ¼ 0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (P ¼ 0.0105, OD ¼ 5.301, 95% CI ¼ 1. 477-19.026) and bladder irrigation (P ¼ 0.0001, OD ¼ 9.469, 95% CI ¼ 3.872-23.156) were significant risk factors of early-onset HC. We conclude that (i) highdose BU as well as CY is a cause of HC, (ii) protective bladder irrigation has an opposite effect, and (iii) Mesna possibly has a toxic effect on bladder mucosa. Bone Marrow Transplantation (2003) 32, 903-907.

Non-small cell lung carcinomas (NSCLC) overexpress the Her2/ /neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/ /neu overexpressing breast cancer. However, its therapeutic use in Her2/ /neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of 64 Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/ /neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with 64 Cu. The molecular specificity of DOTA-trastuzumab was determined in NSCLC cell lines with Her2/ /neu overexpression (NCI-H2170) and negative expression (NCI-H520). Imaging of Her2/ /neu expression was performed in NCI-H2170 tumor-bearing mice with L ung cancer is one of the world's leading causes of death, with a 5-year survival rate of less than 10%.(1) Activation of ras genes and human epidermal growth factor receptor 2 (Her2/neu) genes is encountered in subpopulations of non-small cell lung carcinoma (NSCLC) patients and has been linked to shortened survival. Overexpression of the Her2/neu gene is closely associated with intrinsic multiple drug resistance in NSCLC cell lines.(2) Her2/neu is a transmembrane tyrosine kinase belonging to the surface receptor family. It does not bind ligand but instead acts as a preferred heterodimerization partner for ligand-activated sibling members to amplify mitotic signaling. Trastuzumab, a humanized monoclonal antibody that targets Her2/neu, inhibits neoplastic cell proliferation both in vitro and in vivo.(4) In breast cancer, overexpression of Her2/neu is seen in 40% of cases, and its activation follows heterodimerization with a member of the EGFR family and triggers important biological effects such as proliferation, migration and differentiation.(5) Trastuzumab significantly increases the survival of patients with advanced metastatic breast cancer. Overexpression of Her2/neu is reported in up to 59% of cases of NSCLC and the 2+/3+ overexpression rate is 5-20% in adenocarcinomas.(8-10) As in breast cancer, studies have suggested that the overexpression of Her2/neu in NSCLC is associated with a worse prognosis than negative expression of Her2/ neu. (11,12) The role of trastuzumab targeting Her2/neu expression in the NSCLC has been largely marginalized. Even though NSCLC is usually chemoresistant, the synergistic effect between trastuzumab and chemotherapeutic agents was found to be greater in Her2/neu positive NSCLC than in breast cancer cell lines. (13,14) NSCLC patients with Her2/neu overexpression (3+) in immunohistochemistry (IHC) had better survival when treated with trastuzumab-based therapy than the overall population, but only a small percentage of patients benefited.(10) The marked variation in functional anatomy and pathophysiology within human tumors and within individual patients may account for the high va...

A "wet chemistry" approach for isolation of 211 At from an irradiated bismuth target is described. The approach involves five steps: (1) dissolution of bismuth target in conc. HNO 3 ; (2) removal of the HNO 3 by distillation; (3) dissolution of residue in 8 M HCl; (4) extraction of

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Iron-deficiency anemia (IDA) is a common disease in females of childbearing age. Although iron supplementation quickly improves laboratory-measured parameters, its effect on health-related quality of life is unknown. Here, we conducted a prospective follow-up study to evaluate health-related quality of life in pre-menopausal women diagnosed with IDA. A convenience sample of 92 patients who visited Tokai University Hospital and three other affiliated hospitals were asked to fill out the Medical Outcome Study 36-item short-form health survey (SF-36) during the course of treatment (baseline, and 1 and 3 months after the start of treatment). At baseline, vitality and general health scores were significantly lower than the Japanese national norms. After the start of therapy, however, a significant improvement was seen in all domain scores except role emotional (RE), and at 3 months all eight scores were comparable to or greater than the national norms. In particular, physical functioning and vitality scores of patients with a lower hemoglobin level ( < 9.0 g/dl) at baseline showed a dramatic improvement. Iron supplementation in IDA patients improves not only hemoglobin levels, but also physical function, vitality, and general health perception.

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