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

Abstract

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.

• Authors: Marc Jennewein, Matthew A Lewis, Dawen Zhao, Edward Tsyganov, Nikolai Slavine, Jin He, Linda Watkins, Vikram D Kodibagkar, Sean O'Kelly, Padmakar Kulkarni, Peter P Antich, Alex Hermanne, Frank Rösch, Ralph P Mason, Philip E Thorpe
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 5 Pg. 1377-85 (Mar 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18316558 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Phosphatidylserines
• Radioisotopes
• Arsenic

Topics

• Animals
• Antibodies, Monoclonal (metabolism)
• Arsenic (metabolism)
• Endothelium, Vascular (metabolism)
• Male
• Neovascularization, Pathologic (diagnostic imaging)
• Phosphatidylserines (metabolism)
• Positron-Emission Tomography
• Prostatic Neoplasms (blood supply)
• Radioimmunodetection
• Radioisotopes (metabolism)
• Rats
• Tissue Distribution
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays