Aryl isocyanide derivative for one-pot synthesis of purification-free ^99mTc-labeled hexavalent targeting probe

^99mTc-labeled hexavalent probes can be readily synthesized by the coordination of six equivalent isocyanide ligands towards Tc^I, and alkyl isocyanide ligands have been extensively used for preparing such probes. However, high ligand concentration (>1 mM) is generally required due to their insufficient coordination ability to Tc^I.

In this study, we revealed that aryl isocyanide ligands, which have greater π-accepting ability compared with alkyl ones, provided ^99mTc-labeled hexavalent probes in high radiochemical yields (>95%) even at low ligand concentration (50 μM). We applied this finding to the synthesis of a ^99mTc-labeled hexavalent RGD probe, targeting integrin α_vβ₃. This ^99mTc-labeled probe was prepared in a 5 min reaction at ligand concentration of 50 μM, and exhibited high tumor localization in vivo without post-labeling purification.

The present findings indicate that aryl isocyanide ligands would be a useful precursor to a variety of ^99mTc-labeled hexavalent targeting probes for molecular imaging of saturable systems.

Aryl isocyanide is a better precursor than alkyl isocyanide for preparing ^99mTc-labeled hexavalent targeting probe.

This work provides a straightforward method to prepare molecular imaging agents of high target uptake, which would facilitate nuclear medicine imaging in clinical settings.