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

• Published in: Nuclear medicine and biology Vol. 86-87; pp. 30 - 36
• Main Authors: Mizuno, Yuki, Komatsu, Nagiho, Uehara, Tomoya, Shimoda, Yuka, Kimura, Kohta, Arano, Yasushi, Akizawa, Hiromichi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Inc 01.07.2020; Elsevier BV
• Subjects: 99mTc; Aromatic compounds; Coordination; Cyclic RGD peptide; Imaging; Integrin αvβ3; Isocyanide; Ligands; Localization; Multivalency; Nuclear medicine; Precursors; Probes; Purification; Radiochemistry; Synthesis; Integrin αvβ3; Cyclic RGD peptide; 99mTc; Multivalency; Isocyanide
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2020.05.004

99mTc-labeled hexavalent probes can be readily synthesized by the coordination of six equivalent isocyanide ligands towards TcI, 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 TcI. 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 αvβ3. 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.