⁹⁰Y and¹¹¹In Complexes of a DOTA-Conjugated Integrin α_vβ₃Receptor Antagonist:  Different but Biologically Equivalent

Y-90-TA138 is a Y-90-labeled nonpeptide integrin alpha(v)beta(3) receptor antagonist that binds with high affinity and specificity to integrin alpha(v)beta(3) receptors overexpressed on both endothelial and tumor cells. Y-90-TA138 has demonstrated significant therapeutic effects in several preclinical tumor-bearing animal models. Since Y-90 is a pure beta-emitter, In-111-TA138 has been chosen as the imaging surrogate for dosimetry determination of Y-90-TA138. This report describes the synthesis of In-111-TA138 and biological evaluations of both In-111-TA138 and Y-90-TA138 in the c-neu Oncomouse model. The HPLC data shows that In-111-TA138 is more hydrophilic with the retention time similar to4.5 min shorter than that of Y-90-TA138 under identical chromatographic conditions. Since the only difference between In-111-TA138 and Y-90-TA138 is the metal ion, the HPLC retention time difference strongly suggests that indium and yttrium chelates do not share the same coordination sphere in solution even though they are coordinated by the same DOTA conjugate. Despite their differences in lipophilicity and solution structure, biodistribution data in the c-neu Oncomouse model clearly showed that In-111-TA138 and Y-90-TA138 are biologically equivalent with respect to their uptake in tumors and other major organs. Therefore, In-111-TA138 is useful as an imaging surrogate for Y-90-TA138 and should be able to predict the radiation dosimetry of Y-90-TA138, a therapeutic radiopharmaceutical for treatment of rapidly growing tumors.