Altered biodistribution of indium-111-labeled monoclonal antibody 96.5 to tumors and normal tissues of nude mice bearing human melanoma xenografts in visceral organs.
Human melanoma xenografts were produced in the subcutis, kidney, cecum and liver of different nude mice. An 111In-labeled anti-(human melanoma) monoclonal antibody (96.5) or an 111In-labeled nonspecific control monoclonal antibody (ZCE-025) was injected intravenously in separate groups of mice. Radioactive antibody accumulation was measured in tumor, blood, viscera, and carcasses. mAb 96.5 targeted specifically to tumor tissue regardless of site of growth. Tumors in the liver exhibited significantly (P less than 0.05) higher tumor-to-blood ratios (45 +/- 6, mean +/- SEM) than xenografts at other visceral organs, the lowest value being found for subcutaneous melanoma (2.6 +/- 0.5). The differences in tumor-to-blood ratio were due to significant alterations of antibody biodistribution, since the actual antibody concentration in the different tumor sites was similar. The percentage of recovered anti-melanoma antibody per milliliter of blood in mice with visceral lesions (4.6 +/- 1.1% ml) was significantly lower than that found in mice with subcutaneous tumors (9.5 +/- 1.4%/ml, P less than 0.05). Moreover, significantly higher levels (18.2 +/- 3.2%/g, 31.0 +/- 5.1%/g, respectively) of the melanoma mAb 96.5 were found in normal liver and spleen tissue recovered from mice with visceral tumors as compared to tissue from mice with subcutaneous tumors (9.2 +/- 0.9%/g, 13.5 +/- 1.9%/g, respectively; P less than 0.05). These results demonstrate that the presence of visceral tumor can significantly affect tumor-to-blood ratios, blood levels, and biodistribution of 111In-labeled mAb 96.5.
McCready
D R
DR
Department of General Surgery, M.D. Anderson Cancer Center, Houston 77030.
Price
J
J
Balch
C M
CM
Murray
J L
JL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000378:metabolism*; D000912:Antibodies, Neoplasm / Q000097:blood / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D007205:Indium Radioisotopes / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000097:blood / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000276:immunology; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000097:blood / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014781:Viscera
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007205:Indium Radioisotopes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins