PHARMACOKINETICS OF AN ANTICARCINOEMBRYONIC ANTIGEN MONOCLONAL-ANTIBODY CONJUGATED TO A BIFUNCTIONAL TRANSITION-METAL CARBORANE COMPLEX (VENUS FLYTRAP CLUSTER) IN TUMOR-BEARING MICE

An anticarcinoembryonic antigen (CEA) monoclonal antibody, T84.66, has been conjugated to a metallocarborane complex (Venus flytrap cluster, VFC) containing Co-57. This radioimmunoconjugate, Co-57-VFC-T84.66, r etained >90% immunoreactivity, was stable in serum (7 days) and demons trated good localization in LS174T tumor xenografts. Pharmacokinetics of Co-57-VFC-T84.66 in tumor-bearing mice were compared to T84.66 Mab conjugated with either DTPA or its benzylisothiocyanate derivative (Bz DTPA) labeled with In-111. Whole-body half-life for VFC-T84.66 was les s (t1/2 = 62 hr) than that for either DTPA-T84.66 (t1/2 = 157 hr) or B zDTPA-T84.66 (t1/2 = 167 hr). Blood clearance was similar for all thre e radioimmunoconjugates (t1/2 = 22 hr). Hepatic uptake of the radiolab el was rapid and remained constant for 7 days for both DTPA radioimmun oconjugates (DTPA radioimmunoconjugate = 13.7 +/- 1.5 %ID/g; BzDTPA ra dioimmunoconjugate = 10.4 +/- 1.7 %ID/g). For VFC, however, liver radi oactivity decreased from 19.1 +/- 0.6 %ID/g at 1 hr to 0.9 +/- 0.1 %ID /g 7 days postinjection, suggesting a possible role for VFC radioimmun oconjugate in the imaging and therapy of liver metastases.