COMPARATIVE BIODISTRIBUTION OF INDIUM-LABELED AND YTTRIUM-LABELED B3 MONOCLONAL-ANTIBODY CONJUGATED TO EITHER 2-(P-SCN-BZ)-6-METHYL-DTPA (1B4M-DTPA) OR 2-(P-SCN-BZ)-1,4,7,10-TETRAAZACYCLODODECANE TETRAACETIC ACID (2B-DOTA)

The biodistribution of indium-111/yttrium-88-labeled B3 monoclonal antibody, a murine IgG1k, was evaluated in non-tumor-bearing mice. B3 was conjugated ted to either 2-(p-SCN-Bz)-6-methyl-DTPA (1B4M) or 2-(p-SCN-Bz)-1,4,7,10 tetraazacyclododecane tetra-acetic acid (2B-DOTA) and labeled with In-111 at 1.4-2.4 mCi/mg and Y-88 at 0.1-0.3 mCi/mg. Non-tumor-bearing nude mice were co-injected i.v. with 5-10 mu Ci/4-10 mu g of (111)n/Y-88-labeled B3 conjugates and sacrificed at 6 h and daily up to 168 h post-injection. Mice injected with In-111/Y-88-(1B4M)-B3 showed a similar biodistribution of the two radiolabels in all tissues except the bones, where significantly higher accretion of Y-88 than In-111 was observed, with 2.8% +/- 0.2% vs 1.3% +/- 0.16% ID/g in the femur at 168 h, respectively (P<0.0001). In contrast, mice receiving the In-111/Y-88-(DOTA)-B3 conjugate showed significantly higher accumulation of In-111 than Y-88 in most tissues, including the bones, with 2.0% +/- 0.1% vs 1.2% +/- 0.09% ID/g in the femur at 168 h, respectively (P<0.0001). Whereas the ratios of the areas underneath the curve (%ID x h/g) in the blood, liver, kidney and bone were 0.96, 1.12, 1.13, and 0.74 for In-111/Y-88-(1B4M)-B3 and 0.84, 1.23, 1.56, and 1.31 for In-111/Y-88-(DOTA)-B3, respectively, ratios approximate to 1 were observed between In-111-(1B4M)-B3 and Y-88-(DOTA)-B3. In summary, while neither 1B4M nor DOTA was equally stable for In-111 and Y-88, the fate of Y-88-(DOTA)-B3 could be closely traced by that of In-111-(1B4M)-B3.