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Pharmacokinetics of an Anti-Carcinoembryonic Antigen Monoclonal Antibody Conjugated to a Bifunctional Transition Metal Carborane Complex (Venus Flytrap Cluster) in Tumor-Bearing Mice

Department of General Oncologic Surgery and Division of Radiologic Sciences, City of Hope National Medical Center, Duarte, Canada
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, Canada
Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California

Correspondence: For correspondence and reprints contact: Barbara G. Betty, PhD, Toad Hall, 7 Hermit Ct., Toronto, Ontario, Canada M3B 1R4.

ABSTRACT

An anticarcinoembryonic antigen (CEA) monoclonal antibody, T84.66, has been conjugated to a metallocarborane complex (Venus flytrap cluster, VFC) containing ⁵⁷Co. This radioimmunoconjugate, ⁵⁷Co-VFC-T84.66, retained >90% immunoreactivity, was stable in serum (7 days) and demonstrated good localization in LS174T tumor xenografts. Pharmacokinetics of ⁵⁷Co-VFC-T84.66 in tumor-bearing mice were compared to T84.66 Mab conjugated with either DTPA or its benzylisothiocyanate derivative (BzDTPA) labeled with ¹¹¹In. Whole-body half-life for VFC-T84.66 was less (t_1/2 = 62 hr) than that for either DTPA-T84.66 (t_1/2 = 157 hr) or BzDTPA-T84.66 (t_1/2 = 167 hr). Blood clearance was similar for all three radioimmunoconjugates (t_1/2 = 22 hr). Hepatic uptake of the radiolabel was rapid and remained constant for 7 days for both DTPA radioimmunoconjugates (DTPA radioimmunoconjugate = 13.7 ± 1.5 %ID/g; BzDTPA radioimmunoconjugate = 10.4 ± 1.7 %ID/g). For VFC, however, liver radioactivity 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 radioimmunoconjugate in the imaging and therapy of liver metastases.