In vivo comparison of CHX-DTPA ligand isomers in athymic mice bearing carcinoma xenografts

Monoclonal antibodies (MAbs) labeled with radiometallonuclides via metal ch elators are being investigated in the laboratory for use in clinical trials . The biodistribution of In-111- and Y-88-labeled antibody (MAb B72.3) usin g two isomeric forms (CHX-A and CHX-B) of the 2-(p-isothiocyanatobenzyl)-cy clohexyl-DTPA was compared in athymic mice bearing LS-174T tumors, human co lon carcinoma xenografts. CHX-(A or B)-I-125- DTPA-B72.3 was co-injected in all athymic mice to assess if the chelate conjugation altered the properti es of MAb B72.3. In vitro studies demonstrated maintenance of integrity and immunoreactivity for both radioimmunoconjugates. The in vivo analysis, how ever, indicated major differences between the two isomer forms. In fact, th e Y-88-CHX-A-DTPA radioimmunoconjugate demonstrated over the 7-day study pe riod, a more efficient and stable tumor localization as well as a slower bl ood clearance rate than the CHX-B-DTPA chelate conjugate, suggesting a grea ter in vivo stability. Differences were also evident in critical normal org an uptake: no significant increase in liver- and spleen- or bone-to-blood r atios was observed when the CHX-A-DTPA chelate was labeled with indium or y ttrium. The results described here demonstrate that the CHX-A-DTPA chelate conjugate can be considered move suitable than the CHX-B-DTPA isomer form w hen radiometallonuclides are coupled to an MAb.