title: Pharmacokinetics of an anti-carcinoembryonic antigen monoclonal antibody conjugated to a bifunctional transition metal carborane complex (venus flytrap cluster) in tumor-bearing mice.
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 (t1/2 = 62 hr) than that for either DTPA-T84.66 (t1/2 = 157 hr) or BzDTPA-T84.66 (t1/2 = 167 hr). Blood clearance was similar for all three radioimmunoconjugates (t1/2 = 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.
authors.affiliation: Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, Canada.
authors.forename: B G
authors.initials: BG
authors.lastname: Beatty
authors.forename: R J
authors.initials: RJ
authors.lastname: Paxton
authors.forename: M F
authors.initials: MF
authors.lastname: Hawthorne
authors.forename: L E
authors.initials: LE
authors.lastname: Williams
authors.forename: K J
authors.initials: KJ
authors.lastname: Rickard-Dickson
authors.forename: T
authors.initials: T
authors.lastname: Do
authors.forename: J E
authors.initials: JE
authors.lastname: Shively
authors.forename: J D
authors.initials: JD
authors.lastname: Beatty
mesh_terms: D000818:Animals; D003037:Cobalt Radioisotopes; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D016719:Radioimmunodetection / Q000379:methods*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D003037:Cobalt Radioisotopes; D009942:Organometallic Compounds