Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro

Dearling, Jason L. J.; Lewis, Jason S.; Mullen, Gregory E. D.; Rae, Michael T.; Zweit, Jamal; Blower, Philip J.

Abstract

The well-known perfusion tracer CuPTSM, labelled with 62Cu or 64Cu, is believed to be trapped in cells non-selectively by a bioreductive mechanism. It is proposed that by modifying the ligand to increase its electron donor strength (for example by adding alkyl functionality or replacing sulphur ligands with oxygen ligands), the copper complexes will become less easily reduced and tracers with selectivity for hypoxic tissues could thus be developed. The aim of this work was to prepare 64Cu-labelled complexes of two series of ligands, based on the bis(thiosemicarbazone) (13 ligands) and bis(salicylaldimine) (3 ligands) skeletons, and to evaluate the hypoxia dependence of their uptake in cells. The complexes were incubated with Chinese hamster ovary cells under normoxic and hypoxic conditions, and the cells isolated by centrifugation to determine radioactivity uptake at various time points up to 90 min. Several members of both series demonstrated significant (P

• Journal Article Type: Article
• Publication Date: 1998-07
• Deposit Date: May 12, 2017
• Print ISSN: 1619-7070
• Electronic ISSN: 1619-7089
• Publisher: BMC
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 7
• Pages: 788-792
• DOI: https://doi.org/10.1007/s002590050283
• Keywords: Hypoxia, positron emission tomography.
• Public URL: http://researchrepository.napier.ac.uk/Output/831051