EVALUATION OF THE SERUM STABILITY AND IN-VIVO BIODISTRIBUTION OF CHX-DTPA AND OTHER LIGANDS FOR YTTRIUM LABELING OF MONOCLONAL-ANTIBODIES

Serum stability and in vivo biodistribution of both A and B isomers of the 2-(p-isothiocyanatobenzyl) (p-SCN-Bz)-cyclohexyldiethylenetriamin epentaacetic acid ligand (CHX-DTPA), a recently developed backbone-sub stituted derivative of DTPA, were evaluated and compared to those of 2 -(p-SCN-Bz)-6-methyl-DTPA (1B4M-DTPA) and 2-(p-SCN-Bz)-1,4,7,10-tetraa zacyclododecane tetra-acetic acid (2B-DOTA). Methods: Stability of Y-8 8-labeled ligands (0.1 mu M) was evaluated in serum for up to 17 days. For biodistribution, ligands were conjugated to monoclonal antibody ( Mab) B3, a murine IgG1k, and labeled with Y-88 at 0.1-0.3 mCi/mg. Nont umor-bearing nude mice were injected intravenously with 1-2 mu Ci/4-lO mu g Of Y-88-labeled B3-conjugates and killed at 6 hr and daily up to 168 hr postinjection. Indium-111-(1B4M)-B3 was co-injected in all mic e as internal control. Results: Serum stability of Y-88-DOTA failed to show any significant release of activity, whereas pseudo-first-order dissociation rate constants of 3.97 x 10(-3), 2.54 x 10(-3) and 1.46 x 10(-2) (day(-1)) were calculated for Y-88-1B4M, Y-88-CHX-A and Y-88-C HX-B, respectively. Accordingly, cortical bone uptake of Y-88 was sign ificantly higher for all DTPA-derivative chelates than for DOTA. Concl usions: While none of the DTPA-derivative chelates could challenge DOT A in its ability to hold the radioyttrium, significant differences wer e observed in the kinetic inertness of the A and B isomers of CHX, ind icating that the CHX-B ligand is not as suitable for Y-90-labeling of Mabs.