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

Dearling, Jason L. J. and Lewis, Jason S. and Mullen, Gregory E. D. and Rae, Michael T. and Zweit, Jamal and Blower, Philip J. (1998) Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro. European Journal of Nuclear Medicine, 25 (7). pp. 788-792. ISSN 0340-6997. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1007/s002590050283

Abstract

The well-known perfusion tracer CuPTSM, labelled with Cu-62 or Cu-64 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 Cu-64-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<0.05) or highly significant (P<0.01) hypoxia selectivity, indicating that both series of complexes offer a basis for development of hypoxia-targeting radiopharmaceuticals for positron emission tomography (Cu-60, Cu-61, Cu-62, Cu-64) and targeted radiotherapy (Cu-64, Cu-67).

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: R.F. Xu
Date Deposited: 26 Jun 2009 09:53
Last Modified: 11 Jun 2014 13:45
Resource URI: http://kar.kent.ac.uk/id/eprint/17693 (The current URI for this page, for reference purposes)
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