Synthesis, Radiochemical Characterization, and Biodistribution of a 188Re Analogue of [131I]mIBG in a Neuroblastoma Xenograft Model

Abstract

[¹³¹I]meta-iodobenzylguanidine (mIBG) in variable dosage forms is widely used for the therapy of neuroendocrine tumors. Our group previously reported a ^99mTc analogue of [¹³¹I]mIBG that demonstrated high specificity in vitro towards norepinephrine transporter (NET)–positive neuroblastoma cells. Considering that the ^99mTc/¹⁸⁸Re pair serves as a useful theranostic combination, we herein describe the synthesis of its ¹⁸⁸Re analogue and evaluate its potential for therapeutic applications. A benzylguanidine derivative functionalized at the meta position via an isonitrile moiety (“1”) was employed for ¹⁸⁸Re complexation following Re-“4 + 1” chemistry. Synthesized ¹⁸⁸Re complex 6 was evaluated in NET-positive SK-N-SH neuroblastoma cells and corresponding xenograft models. Cellular uptake studies revealed that the ¹⁸⁸Re complex 6 exhibited ~50% of the uptake observed for [¹²⁵I]mIBG. Nonetheless, it retained significant NET specificity (~60%), as confirmed by inhibition experiments using desmethylimipramine (DMI). Biodistribution studies in SK-N-SH xenograft-bearing mice demonstrated tumor uptake of 4.07 ± 0.08%ID/g at 30 min (p > 0.05), with significant retention up to 3 h (4.99 ± 0.08%ID/g). Tumor uptake was shown to be NET-specific, as pre-treatment with excess DMI significantly inhibited tracer accumulation in vivo. Bioevaluation of the synthesized ¹⁸⁸Re complex 6 confirmed its affinity for NETs; however, limited in vivo stability restricted its suitability for therapeutic application.