90Y and 111In Complexes of a DOTA-Conjugated Integrin αvβ3 Receptor Antagonist: Different but Biologically Equivalent

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Abstract
90Y-TA138 is a 90Y-labeled nonpeptide integrin αvβ3 receptor antagonist that binds with high affinity and specificity to integrin αvβ3 receptors overexpressed on both endothelial and tumor cells. 90Y-TA138 has demonstrated significant therapeutic effects in several preclinical tumor-bearing animal models. Since 90Y is a pure β-emitter, 111In-TA138 has been chosen as the imaging surrogate for dosimetry determination of 90Y-TA138. This report describes the synthesis of 111In-TA138 and biological evaluations of both 111In-TA138 and 90Y-TA138 in the c-neu Oncomouse model. The HPLC data shows that 111In-TA138 is more hydrophilic with the retention time ∼4.5 min shorter than that of 90Y-TA138 under identical chromatographic conditions. Since the only difference between 111In-TA138 and 90Y-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 111In-TA138 and 90Y-TA138 are biologically equivalent with respect to their uptake in tumors and other major organs. Therefore, 111In-TA138 is useful as an imaging surrogate for 90Y-TA138 and should be able to predict the radiation dosimetry of 90Y-TA138, a therapeutic radiopharmaceutical for treatment of rapidly growing tumors.

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