DO2A-based ligands for gallium-68 chelation: synthesis, radiochemistry and cardiac uptake

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 49; no. 4; pp. 197 - 116
• Main Authors: Smith, Adam J, Osborne, Bradley E, Keeling, George P, Blower, Philip J, Southworth, Richard, Long, Nicholas J
• Format: Journal Article
• Language: English
• Published: 28.01.2020
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c9dt02354b

Radiolabelled lipophilic cations could potentially be used to non-invasively image mitochondrial dysfunction in cardiovascular disease, building on their current role as perfusion imaging agents. We have synthesised and radiolabelled two series of DO2A-based radiotracers, with bistriarylphosphonium- and bisaryl-functionalisation respectively, with gallium-68 to form lipophilic cations. Both sets of tracers radiolabel with over 90% RCP, although the tracers form kinetic/thermodynamic pairs of species upon gallium chelation that can be visualised and separated by radioHPLC. Log  D 7.4 values above −0.3 are observed for the most lipophilic examples of each series of radiotracers. Both tracers show significant preferential uptake in healthy cardiac tissue over cardiac tissue depolarised by CCCP. New DO2A-based lipophilic and cationic chelators for gallium-68 have been synthesised for cardiac PET imaging. These radiotracers show preferential uptake in healthy cardiac tissue over cardiac tissue depolarised by CCCP.