In vivo evaluation of bismuth-labeled monoclonal antibody comparing DTPA-derived bifunctional chelates

Among the radionuclides considered for radioimmunotherapy, alpha -emitters such as the bismuth isotopes, Bi-212 and Bi-213, are of particular interest . The macrocyclic ligand, DOTA, has been shown to form stable complexes wit h bismuth isotopes. The kinetics of the complexation of bismuth with the DO TA chelate, however, are slow and impractical for use with Bi-212 and Bi-21 3 that have half-lilies of 60.6 and 45.6 min. The study described herein co mpares six DTPA derived bifunctional chelates with the goal of identifying an alternative to the DOTA ligand for radiolabeling with bismuth. Radioimmu noconjugates comprised of MAb B72.3, each of the six DTPA chelates, and rad iolabeled with Bi-206, which facilitated the evaluation due to its readily detectable gamma -emission. In vitro studies showed that each of rite radio immunoconjugates retained immunoreactivity that was comparable to its I-125 -labeled counterpart. The Bi-206- and I-125-labeled immunoconjugates were t hen co-injected i.p. into normal athymic mice. injection of Afree@ Bi-206 d emonstrated that the kidneys were the critical organ to evaluate for retent ion of bismuth in the chelate complex. Major differences were identified am ong the six preparations. The CHX-A and -B immunoconjugates were found to h ale 1) the lowest %ID/gm in the kidney; 2) a level of Bi-206 in the kidney that was comparable to that of I-125-B72.3; and 3) Ilo significant uptake o f Bi-206 evident In other organs such as bone, lung and spleen. The results described her-ein suggest that either of the cyclohexyl derivatives of DTP A may be suitable candidates for the labeling of immunoconjugates with alph a -emitting bismuth isotopes for radioimmunotherapeutic applications.