Localization of 131I-labeled antibodies in human renal cell carcinomas and in a mouse hepatoma and correlation with tumor detection by photoscanning.

Abstract

Xenogeneic anti-human renal cell carcinoma globulins (ARCG's), which had been rendered tumor specific by absorptions with normal human tissues, reacted on immunofluorescence with smears and sections of 21 of 22 human renal cell carcinomas tested, but not with any adult, normal human tissues, including kidney. The i.v. administration of 131I-labeled ARCG followed by photoscanning visualized 13 of 15 primary renal cell carcinomas and metastases in 7 of 8 patients. Immunofluorescence and autoradiography of sections and dissociated cells revealed more ARCG and radioactivity bound to tumor tissue than to adjacent normal tissue. However, assay of tissue digests showed more radioactivity in primary carcinoma than in adjacent renal tissue in five patients, similar amounts in both areas in two patients, and less radioactivity in tumor in another five cases. Correlation of scanning with the extent of tumor localization of 131I showed that all tumors which contained equal or greater radioactivity than did normal kidney, and three of five containing less radioactivity, were successfully imaged. The s.c. transplants of the mouse H6 hepatoma were visualized by 131I-labeled anti-tumor globulin prepared by a method identical to that for ARCG. If anti-tumor globulin was further purified, a 2-fold increase in the tumor:blood ratio of radioactivity was obtained, but only minor improvement in the quality of scans. 131I-labeled normal rabbit globulin failed to visualize tumors, and 67Ga citrate scanning could not discriminate between hepatoma transplants and Freund's complete adjuvant-induced granulomas. The tumor specificity of 131I-labeled anti-tumor globulins as imaging agents is supported by: ( a ) the failure of normal rabbit globulin and 99mTc-sulfur colloid to image the hepatoma and renal carcinoma, respectively; ( b ) the immunofluorescence and autoradiography evidence that i.v.-administered 131I-ARCG localized in and bound firmly to tumor tissue, but not to adjacent renal tissue; and ( c ) the fact that the tumor which did not bind 131I-ARCG could not be visualized. It appears that the success of 131I-labeled anti-tumor globulins as imaging agents is associated with their specific tumor localization but can be aided by such nonspecific factors as increased and more permeable tumor vasculature.