['The trapping mechanisms of the PET hypoxia imaging agent copper(II)-diacetyl-bis(N (4)-methylthiosemicarbazone) ((64)Cu(ATSM)) remain unresolved, although its reduction prior to dissociation may be mediated by intracellular thiols. Glutathione (GSH) is the most abundant intracellular thiol, and its redox status changes in cancer cells and ischaemic myocardium (two prime applications for (64)Cu(ATSM) PET). We therefore investigated whether modification of intracellular GSH content affects the hypoxia selectivity of (64)Cu(ATSM).', 'Isolated rat hearts (n\u2009=\u2009five per group) were perfused with aerobic buffer (equilibrated with 95%O2/5%CO2) for 15\xa0min, then hypoxic buffer (95%N2/5%CO2) for 20\xa0min. Cardiac glutathione was depleted by buthionine sulphoximine (BSO, 4\xa0mmol/kg/ 48\xa0h intraperitoneal), or augmented by N-acetyl cysteine (NAC, 4\xa0mmol/L) in the perfusion buffer. Cardiac (64)Cu retention from three 2-MBq bolus injections of (64)Cu(ATSM) before and during hypoxia was then monitored by NaI detectors.', 'Cardiac GSH content was elevated by NAC and depleted by BSO (from 7.9\u2009±\u20092.0 to 59.3\u2009±\u20098.3\xa0nmol/mg and 3.7\u2009±\u20091.0\xa0nmol/mg protein, respectively; p\u2009<\u20090.05). Hypoxia did not affect cardiac GSH content in any group. During normoxia, tracer washed out bi-exponentially, with 13.1%\u2009±\u20091.7% injected dose being retained; this was not affected by GSH augmentation or depletion. Hypoxia significantly increased tracer retention (to 59.1%\u2009±\u20096.3%, p\u2009<\u20090.05); this effect was not modified by GSH augmentation or depletion.'] Does modification of intracellular glutathione status change the cardiac trapping of ( 64 ) Cu ( ATSM )?