Preclinical evaluation of 111In-labeled B3 monoclonal antibody: biodistribution and imaging studies in nude mice bearing human epidermoid carcinoma xenografts.
Biodistribution and imaging characteristics of monoclonal antibody B3 were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. B3 is a murine IgG1k, recently isolated, reacting with a carbohydrate epitope abundantly and uniformly expressed by most carcinomas. B3 was conjugated to a new backbone-substituted derivative of diethylenetriaminepentaacetic acid, 2-(p-isothiocyanato benzyl)-cyclohexyl-diethylenetriaminepentaacetic acid, and labeled with 111In. Tumor-bearing mice were given i.v. injections of approximately 5 microCi of either 111In-B3 or 111In-MOPC-21, an isotype-matched control, and sacrificed in groups of five at 6 h and daily up to 168 h. Imaging was performed at 24, 72, and 144 h. Significant differences were observed in tumor uptake at all time points with peak values at 48 h (25 +/- 5.2% versus 6.3 +/- 0.4% of the injected dose/g tissue) (mean +/- SD) for 111In-B3 and 111In-MOPC-21, respectively (P < 0.001). All tumor to organ ratios increased with time for 111In-B3. In particular, tumor:liver ratios rose from 3.2 +/- 0.6 at 24 h to 6.3 +/- 1.2 at 168 h. Imaging results showed selective and progressive accumulation of 111In-B3 at the tumor site, whereas 111In-MOPC-21 did not show specific localization. In summary, 111In-labeled B3 demonstrated good and specific tumor targeting, which warrants its future clinical evaluation.
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Cancer Institute, NIH, Bethesda, Maryland 20892.
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Camera
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Kinuya
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Pai
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Garmestani
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Brechbiel
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Gansow
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Paik
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Pastan
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Carrasquillo
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D016719:Radioimmunodetection; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007205:Indium Radioisotopes