PHARMACOKINETICS OF AN INDIUM-111-LABELED MONOCLONAL-ANTIBODY IN CANCER-PATIENTS

Abstract

The pharmacokinetics were evaluated in patients of a monoclonal antibody (19-9) F(ab'')2 fragment coupled with DTPA [diethylenetriamine pentaacetic acid] and labeled with 11In. In addition to imaging and organ uptake determinations, serum and urine samples were analyzed to help determine the in vivo behavior of the label. Using a competitive binding assay, the immunoreactivity of the coupled fragment was found to be indistinguishable from that of the unmodified fragment. The absence of radiocolloids in the injectate was confirmed as was the in vivo stability of the attached DTPA groups. By a variety of techniques, it was shown that the only significant source of label instability was transcomplexation to circulating transferrin. About 9%/day of label exposed to transferrin (.apprx. 1-2% of the injected dose) dissociated with slight bone marrow accumulation. Following i.v. administration, serum activity levels fell rapidly (T1/2.alpha. 2 h, T1/2.beta. 19 h). Whole-body clearance of the label was slow (T1/2 160 h) and may be attributed entirely to urinary excretion (0.26% of the injected dose per h). Organ accumulation was greatest in the liver and persisted after rapidly attaining high values (20% of the injected dose). A total of 14 cancer patients were studied, 9 with identifiable sites of metastatic disease from colorectal [8], pancreatic [2], ovarian [3], or small cell lung [1] primaries. Eight of the 12 sites of documented tumor were visualized by external imaging (67%) most distinctly at 48-72 h postadministration. [The diagnostic and therapeutic applications of monoclonal antibodies are discussed.].