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Vascular Imaging of Solid Tumors in Rats with a Radioactive Arsenic-Labeled Antibody that Binds Exposed Phosphatidylserine

Authors' Affiliations: ¹ Institute of Nuclear Chemistry, Johannes Gutenberg-University of Mainz, Mainz, Germany; ² Cancer Imaging Program, Department of Radiology, ³ Simmons Cancer Center, and ⁴ Department of Pharmacology and Hamon Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; ⁵ VUB Cyclotron, University of Brussels, Brussels, Belgium; and ⁶ Department of Nuclear Engineering, University of Texas at Austin, Pickle Research Campus, Austin, Texas

Requests for reprints: Philip E. Thorpe, Department of Pharmacology and Simmons and Hamon Cancer Centers, University of Texas Southwestern Medical Center at Dallas, 2201 Inwood Road NC7.304, Dallas, Texas 75390-8794. Phone: 214-648-1499; Fax: 214-648-1613; E-mail: Philip.Thorpe{at}utsouthwestern.edu.

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 ⁷⁴As (β⁺, T_1/2 17.8 days) or ⁷⁷As (β^–, 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 -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.