Purpose: We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats. As (h -,T 1/2 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1tumors in rats. Results: Clear images of the tumors were obtained using planar g-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium. Conclusions: These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.
72 As, 74 As, 77 As / Radioactive arsenic / Germanium target / Radiochemical separation / Labelled antibodies Summary. Radioarsenic labelled radiopharmaceuticals could add special features to molecular imaging with positron emission tomography (PET). For example the long physical half-lives of 72 As (T 1/2 = 26 h) and 74 As (T 1/2 = 17.8 d) in conjunction with their high positron branching rates of 88% and 29%, respectively, allow the investigation of slow physiological or metabolical processes, like the enrichment and biodistribution of monoclonal antibodies in tumour tissue or the characterization of stem cell trafficking. A method for separation and purification of no-carrier-added (nca) arsenic from irradiated metallic germanium targets based on distillation and anion exchange is developed. It finally converts the arsenic into an * As(III) synthon in PBS buffer and pH 7 suitable for labelling of proteins via As−S bond formations. The method delivers radioarsenic in high purity with separation factors of 10 6 from germanium and an overall yield from target to labelling synthon of > 40%. In a proof-ofprinciple experiment, the monoclonal antibody Bevacizumab, directed against the human VEGF receptor, was labelled with a radiochemical yield > 90% within 1 h at room temperature with nca 72/74/77 As.
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