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

• Published in: Nuclear medicine and biology Vol. 86-87; p. 30
• Main Authors: Mizuno, Yuki, Komatsu, Nagiho, Uehara, Tomoya, Shimoda, Yuka, Kimura, Kohta, Arano, Yasushi, Akizawa, Hiromichi
• Format: Journal Article
• Language: English
• Published: United States 16.05.2020
• Subjects: (99m)Tc; Multivalency; Cyclic RGD peptide; Integrin α(v)β; Isocyanide
• ISSN: 1872-9614

Tc-labeled hexavalent probes can be readily synthesized by the coordination of six equivalent isocyanide ligands towards Tc , 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 . In this study, we revealed that aryl isocyanide ligands, which have greater π-accepting ability compared with alkyl ones, provided Tc-labeled hexavalent probes in high radiochemical yields (>95%) even at low ligand concentration (50 μM). We applied this finding to the synthesis of a Tc-labeled hexavalent RGD probe, targeting integrin α β . This Tc-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 Tc-labeled hexavalent targeting probes for molecular imaging of saturable systems. Aryl isocyanide is a better precursor than alkyl isocyanide for preparing Tc-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.