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

Marc Jennewein, Matthew A. Lewis, Dawen Zhao, Edward Tsyganov, Nikolai Slavine, Jin He, Linda Watkins, Vikram Kodibagkar, Sean O'Kelly, Padmakar Kulkarni, Peter P. Antich, Alex Hermanne, Frank Rösch, Ralph P. Mason, Philip E. Thorpe

Research output: Contribution to journalArticle

75 Citations (Scopus)

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 74As (β+,T1/2 17.8 days) or 77As (β-,T1/2 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 γ-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.

Original languageEnglish (US)
Pages (from-to)1377-1385
Number of pages9
JournalClinical Cancer Research
Volume14
Issue number5
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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Phosphatidylserines
Arsenic
Blood Vessels
Antibodies
Neoplasms
Radioisotopes
Molecular Imaging
Tumor Microenvironment
Antibody Specificity
Vascular Endothelium
Radionuclide Imaging
Positron-Emission Tomography
Prostate
Phospholipids
Oxidative Stress
Research Design
Endothelial Cells
Monoclonal Antibodies
bavituximab
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vascular imaging of solid tumors in rats with a radioactive arsenic-labeled antibody that binds exposed phosphatidylserine. / Jennewein, Marc; Lewis, Matthew A.; Zhao, Dawen; Tsyganov, Edward; Slavine, Nikolai; He, Jin; Watkins, Linda; Kodibagkar, Vikram; O'Kelly, Sean; Kulkarni, Padmakar; Antich, Peter P.; Hermanne, Alex; Rösch, Frank; Mason, Ralph P.; Thorpe, Philip E.

In: Clinical Cancer Research, Vol. 14, No. 5, 01.03.2008, p. 1377-1385.

Research output: Contribution to journalArticle

Jennewein, M, Lewis, MA, Zhao, D, Tsyganov, E, Slavine, N, He, J, Watkins, L, Kodibagkar, V, O'Kelly, S, Kulkarni, P, Antich, PP, Hermanne, A, Rösch, F, Mason, RP & Thorpe, PE 2008, 'Vascular imaging of solid tumors in rats with a radioactive arsenic-labeled antibody that binds exposed phosphatidylserine', Clinical Cancer Research, vol. 14, no. 5, pp. 1377-1385. https://doi.org/10.1158/1078-0432.CCR-07-1516
Jennewein, Marc ; Lewis, Matthew A. ; Zhao, Dawen ; Tsyganov, Edward ; Slavine, Nikolai ; He, Jin ; Watkins, Linda ; Kodibagkar, Vikram ; O'Kelly, Sean ; Kulkarni, Padmakar ; Antich, Peter P. ; Hermanne, Alex ; Rösch, Frank ; Mason, Ralph P. ; Thorpe, Philip E. / Vascular imaging of solid tumors in rats with a radioactive arsenic-labeled antibody that binds exposed phosphatidylserine. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 5. pp. 1377-1385.
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AU - Lewis, Matthew A.

AU - Zhao, Dawen

AU - Tsyganov, Edward

AU - Slavine, Nikolai

AU - He, Jin

AU - Watkins, Linda

AU - Kodibagkar, Vikram

AU - O'Kelly, Sean

AU - Kulkarni, Padmakar

AU - Antich, Peter P.

AU - Hermanne, Alex

AU - Rösch, Frank

AU - Mason, Ralph P.

AU - Thorpe, Philip E.

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N2 - 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+,T1/2 17.8 days) or 77As (β-,T1/2 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 γ-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.

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