title: Evaluation of a new DTPA-derivative chelator: comparative biodistribution and imaging studies of 111In-labeled B3 monoclonal antibody in athymic mice bearing human epidermoid carcinoma xenografts.
abstract: Biodistribution and imaging characteristics of monoclonal antibody (MAb) B3 conjugated to either the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA (CHX-B) or 2-(p-isothiocyanatobenzyl)-6-methyl-DTPA (1B4M) and labeled with 111In, were evaluated in nude mice bearing A431 human epidermoid carcinoma xenografts. MAb B3, is a murine IgG1k reacting with a carbohydrate antigen abundantly expressed by most carcinomas. Both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3 showed good tumor targeting with peak values observed at 72 h with 27.6 +/- 7.6 and 25.4 +/- 1.7% ID/g, respectively (P > 0.05). High tumor-to-organ ratios were also observed and, confirmed by the imaging results. In particular, tumor-to-liver ratios increased from 5.0 +/- 0.9 at 24 h to 9.2 +/- 2.0 at 168 h for 111In-(CHX-B)-B3 and from 4.5 +/- 0.6 to 8.9 +/- 3.5 for 111In-(1B4M)-B3. This was mainly the result of low liver accumulation of both 111In-(CHX-B)-B3 and 111In-(1B4M)-B3, with only 2.48 +/- 0.46 and 2.5 +/- 0.9% ID/g at 168 h, respectively (P > 0.05). Our findings indicate that either CHX-B or 1B4M can be successfully used for 111In-labeling of MAbs and that 111In-B3 may represent a promising radioimmunoimaging agent.
authors.affiliation: Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
authors.forename: L
authors.initials: L
authors.lastname: Camera
authors.forename: S
authors.initials: S
authors.lastname: Kinuya
authors.forename: K
authors.initials: K
authors.lastname: Garmestani
authors.forename: L H
authors.initials: LH
authors.lastname: Pai
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: O A
authors.initials: OA
authors.lastname: Gansow
authors.forename: C H
authors.initials: CH
authors.lastname: Paik
authors.forename: I
authors.initials: I
authors.lastname: Pastan
authors.forename: J A
authors.initials: JA
authors.lastname: Carrasquillo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002614:Chelating Agents / Q000493:pharmacokinetics*; D004355:Drug Stability; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism*; D007205:Indium Radioisotopes; D017879:Isothiocyanates / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D000922:Immunotoxins; D007205:Indium Radioisotopes; D017879:Isothiocyanates; C077295:2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; D004369:Pentetic Acid