Evaluation of the in vivo biodistribution of yttrium-labeled isomers of CHX-DTPA-conjugated monoclonal antibodies

We evaluated the in vivo stability and biodistribution of four isomers (CHX-A', CHA-A, CHX-B' and CHX-B) of 2-(p-isothiocyanato-benzyl)-cyclohexyl-diethylenetriaminepentaacetic acid (CHX-DTPA), a recently developed backbone-substituted derivative of DTPA. Methods: The ligands were conjugated to monoclonal antibody B3, a murine IgG1 kappa, and labeled with 88 Y at 55.5-66.6 MBq/mg (1.5-1.8 mCi/mg). Nontumor-bearing nude mice were injected intravenously with 55.5-66.6 kBq (1.5-1.8 μCi) of 88 Y-labeled B3 conjugates and with 125 I-labeed B3 as an internal control. The mice were then killed at 6, 24, 48, 96 and 168 hr postinjection. Results: At 168 hr, the concentration of 88 Y in processed bone of either CHX-A' [4.6% injected dose (ID)/g] or CHX-A (4.0%ID/g) was less than that of either the CHX-B' (21.9%ID/g) or B (12.1%ID/g) ligands. The two ligands CHX-B and CHX-B' were not acceptable for yttrium labeling of antibody because of their high and progressive bone accumulation. The accumulation of 88 Y in bone of CHX-B' was five times greater than that of CHX-A' at 168 hr. The CHX-A cleared from the circulation slightly faster than CHX-A' without releasing the yttrium and showed the lowest uptake by bone of any of the four isomers. The accumulation in the other normal organs was similar for all four isomers of 88 Y-CHX-B3 conjugates. Conclusion: Although the CHX-B and CHX-B' were not acceptable for labeling with yttrium, the CHX-A' and CHX-A were suitable, indicating that differences in stereochemistry can greatly influence stability of radionuclide in the chelate.