Vascular imaging of solid tumors in rats with a radioactive arsenic-labeled antibody that binds exposed phosphatidylserine.

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. EXPERIMENTAL DESIGN: Bavituximab was labeled with (74)As (beta(+), T(1/2) 17.8 days) or (77)As (beta(-), 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-AT1 tumors in rats. RESULTS: Clear images of the tumors were obtained using planar gamma-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.

Refractive-index changes caused by proton radiation in silicate optical glasses.

We have studied experimentally, by using a differential interferometric technique, the effect of proton radiation on the refractive index of commercial (Schott) silicate crown glasses, BK7 and LaK9, and their radiation-resistant counterparts. The strongest effect was observed for the radiation-hard lanthanum crown LaK9G15: At a 0.65-Mrad dose the index change was approximately 3 x 10(-5). Radiation-hard glasses are used in optical systems operating in radiation environments because they prevent spectral transmission degradation in the visible. However, such glasses are not protected against radiation-induced refractive-index perturbations, and a diffraction-limited optical system based on such glasses may fail owing to radiation-induced aberrations.