DO2A-based ligands for gallium-68 chelation: Synthesis, radiochemistry and: Ex vivo cardiac uptake

Adam J. Smith; Bradley E. Osborne; George P. Keeling; Philip J. Blower; Richard Southworth; Nicholas J. Long

doi:10.1039/c9dt02354b

DO2A-based ligands for gallium-68 chelation: Synthesis, radiochemistry and: Ex vivo cardiac uptake

Adam J. Smith, Bradley E. Osborne, George P. Keeling, Philip J. Blower, Richard Southworth^*, Nicholas J. Long

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	1097-1106
Number of pages	10
Journal	Dalton Transactions
Volume	49
Issue number	4
DOIs	https://doi.org/10.1039/c9dt02354b https://doi.org/C8DT02966K
Publication status	Published - 1 Jan 2020

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10.1039/c9dt02354b
C8DT02966KLicence: CC BY-ND

Smith 68Ga lipophilic cations daltons 2018Accepted author manuscript, 775 KBLicence: CC BY-ND

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abstract = "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 D7.4 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.",

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T2 - Synthesis, radiochemistry and: Ex vivo cardiac uptake

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AU - Osborne, Bradley E.

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AU - Blower, Philip J.

AU - Southworth, Richard

AU - Long, Nicholas J.

PY - 2020/1/1

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AB - 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 D7.4 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.

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DO2A-based ligands for gallium-68 chelation: Synthesis, radiochemistry and: Ex vivo cardiac uptake

Abstract

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