Synthesis, Radiochemical Characterization, and Biodistribution of a 188 Re Analogue of 131 ImIBG in a Neuroblastoma Xenograft Model

ABSTRACT 131 Imeta‐iodobenzylguanidine (mIBG) in variable dosage forms is widely used for the therapy of neuroendocrine tumors. Our group previously reported a 99m Tc analogue of 131 ImIBG that demonstrated high specificity in vitro towards norepinephrine transporter (NET)–positive neuroblastoma cells. Considering that the 99m Tc/ 188 Re pair serves as a useful theranostic combination, we herein describe the synthesis of its 188 Re analogue and evaluate its potential for therapeutic applications. A benzylguanidine derivative functionalized at the meta position via an isonitrile moiety (“ 1 ”) was employed for 188 Re complexation following Re‐“4 + 1” chemistry. Synthesized 188 Re complex 6 was evaluated in NET‐positive SK‐N‐SH neuroblastoma cells and corresponding xenograft models. Cellular uptake studies revealed that the 188 Re complex 6 exhibited ~50% of the uptake observed for 125 ImIBG. 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 188 Re complex 6 confirmed its affinity for NETs; however, limited in vivo stability restricted its suitability for therapeutic application.