This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andersson, H. Articles by Palm, S. Search for Related Content PubMed PubMed Citation Articles by Andersson, H. Articles by Palm, S.

Astatine-211-labeled Antibodies for Treatment of Disseminated Ovarian Cancer

An Overview of Results in an Ovarian Tumor Model¹

Departments of Oncology [H. A., G. H., R. H.] and Radiation Physics [J. E., L. J., B. K., S. L., S. P.], Sahlgrenska University Hospital, Göteborg University, SE 413 45 Göteborg, Sweden; Positron Emission Tomography and Cyclotron Unit, DK 2100 Copenhagen, Denmark [H. J.]; and Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [S. P.]

Purpose: The aim of the study was to establish and refine a preclinical model to -immunoradiotherapy of ovarian cancer.

Experimental Design: At-211 was produced by cyclotron irradiation of a bismuth-209 target and isolated using a novel dry distillation procedure. Monoclonal antibodies were radiohalogenated with the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate and characterized in terms of radiochemical yield and in vitro binding properties. In vitro OVCAR-3 cells were irradiated using an external Cobalt-60 beam, as reference, or At-211-albumin and labeled antibody. Growth assays were used to establish cell survival. A Monte Carlo program was developed to simulate the energy imparted and the track length distribution. Nude mice were used for studies of WBC depression, with various activities of Tc-99m antibodies, as reference, and At-211 antibodies. In efficacy studies, OVCAR-3 cells were inoculated i.p., and animals were treated 2 weeks later. The animals were either dissected 6 weeks later or followed-up for long-term survival.

Results: A rapid distillation procedure, as well as a rapid and high-yield, single-pot labeling procedure, was achieved. From growth inhibition data, the relative biological effectiveness of the -emission for OVCAR-3 cells was estimated to be approximately 5, which is in the same range as found in vivo for hematological toxicity. At-211 MOv18 was found to effectively inhibit the development of tumors and ascites, also resulting in long-term survival without significant toxic effect.

Conclusions: Use of the short-range, high-linear energy transfer -emitter At-211 conjugated to a surface epitope-recognizing monoclonal antibody appears to be highly efficient without significant toxicity in a mouse peritoneal tumor model, urging a Phase I clinical trial.

This article has been cited by other articles:

				S. Lindegren, S. Frost, T. Back, E. Haglund, J. Elgqvist, and H. Jensen Direct Procedure for the Production of 211At-Labeled Antibodies with an {varepsilon}-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugate J. Nucl. Med., September 1, 2008; 49(9): 1537 - 1545. [Abstract] [Full Text] [PDF]

				M. R. Zalutsky Targeted {alpha}-Particle Therapy of Microscopic Disease: Providing a Further Rationale for Clinical Investigation J. Nucl. Med., August 1, 2006; 47(8): 1238 - 1240. [Full Text] [PDF]

				E. Dadachova, T. Burns, R. A. Bryan, C. Apostolidis, M. W. Brechbiel, J. D. Nosanchuk, A. Casadevall, and L. Pirofski Feasibility of Radioimmunotherapy of Experimental Pneumococcal Infection Antimicrob. Agents Chemother., May 1, 2004; 48(5): 1624 - 1629. [Abstract] [Full Text] [PDF]