Comparison of yttrium and indium complexes of DOTA-BA and DOTA-MBA:: Models for 90Y- and 111In-labeled DOTA-biomolecule conjugates

Yttrium and indium complexes of 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetyl-benzylamine (DOTA-BA) and 1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecylacetyl-R-(+)-alpha-methylbenzylamine (DOTA-MBA) were prepared in order to study solution structures of Y-90- and In-111-labeled DOTA-biomolecule conjugates. Y-90 and In-111 complexes M(L) (M = Y-90 and In-111; L = DOTA-BA and DOTA-MBA) were prepared from the reaction Of MCl3 with DOTA-BA and DOTA-MBA, respectively, in ammonium acetate buffer. A reverse phase HPLC method revealed that both Y-90 and In-111 complexes show Only one radiometric peak in their radio-HPLC chromatograms. It was also found that In-111(DOTA-BA) and In-111(DOTA-MBA) are more hydrophilic than their corresponding Y-90 analogues, suggesting different coordination spheres in In-111 and Y-90 complexes of the same DOTA conjugate. Complexes M(L) (M = Y and In; L = DOTA-BA and DOTA-MBA) were prepared and characterized by HPLC, LC-MS, and NMR (H-1 and C-13) methods. The HPLC concordance experiments for Y-90(DOTA-MBA)[Y(DOTA-MBA) and In-111(DOTA-MBA)/In(DOTA-MBA) show that the same complex is prepared at both tracer and macroscopic levels. The NMR data (H-1 and C-13) clearly demonstrates that Y(DOTA-BA) and Y(DOTA-MBA) exist in solution as one predominant isomer. VT NMR data (H-1 and C-13) show that In(DOTA-BA) and In(DOTA-MBA) are fluxional at room temperature while Y(DOTA-BA) and Y(DOTA-MBA) become fluxional only at elevated temperatures. The fluxionality of these complexes is due to rapid rotation of acetate/acetamide chelating arms and inversion of ethylenic groups of the macrocyclic ring.