Pharmacokinetics, Biodistribution, and Gamma Camera Imaging of '"In-KC-4G3 Murine Monoclonal Antibody in Athymic Nude Mice with or without Human Tumor Xenografts1

The pharmacokinetics and tissue distribution of the monoclonal anti body radioconjugate '"In-diethylcnetriaminepentaacetic acid-KC-4G3, which is directed against a high molecular »eight mucin(s) antigen expressed on the human milk fat globule and many epithelial cell mem branes, were examined in BALB/c nude mice with and without xenografts of the human tumor lines ZR-75 (mammary adenocarcinoma, KC-4G3 antigen positive) and BALL-1 (B-cell lymphoma, KC-4G3 antigen nega tive). Plasma of ZR-75 and BALL-1 tumor-bearing nude mice inoculated with '"In-KC-4G3 had a higher initial volume of distribution (f7,), steady state volume of distribution ( <,j. and plasma clearance and a lower initial half-life u.i than non-tumor-bearing nude mice. There were no signifi cant differences in biological half-life u ) in tumorand non-tumorbearing nude mice. Urinary and fecal excretion of radioactivity by ZR75 tumor-bearing mice was greater than that of BALL-1 and non-tumorbearing mice. Localization of "'In-KC-4G3 in mice bearing xenografts of ZR-75 was significantly greater than in mice with BALL-1 tumors. Uptake of '"In-KC-4G3 by ZR-75 tumors averaged 14% of injected dose/g at 72 h after inoculation and was unaffected by antibody dose. Significantly, the radioconjugate concentration in ZR-75 tumors remained relatively constant from 72 to 336 h post-inoculation, while that in normal tissues declined considerably over this period. Nonspecific reticuloendothelial tissue uptake of '"In-KC-4G3 was only moderately affected by pretreatment with a large excess of unlabeled normal mouse immunoglobulin and was not changed by treatment with asialofetuin. Further enhancement of specific localization of '"In-KC-4G3 was obtained by subtraction of the blood pool identified by co-inoculation of '"I-labeled, isotype-identical. normal mouse immunoglobulin. Gamma camera images of'"In-KC-4G3-inoculated ZR-75 tumor-bearing mice showed enhanced tumor localization compared to mice with BALL-1 tumors. The results of this study suggest that '"In-KC-4G3 may prove useful for imaging and possibly therapy of human malignancies expressing the high molec ular weight epithelial mucin(s).