We studied the biodistribution and tumour localization of Tc-99(m)-labelled-5-thio-D-glucose (Tc-99(m)-TG). 5-Thio-D-glucose was labeled with Tc-99(m) by direct stannous ion reduction. The biodistribution of Tc-99(m)-TG was investigated in normal rabbits and in mice bearing experimental tumours. In rabbits, the plasma and clearance of Tc-99(m)-TG was 14.5 +/- 2.0 and 11.3 +/- 3.0 ml.min(-1) respectively. Urinary excretion at 1 h was 53 +/- 5%. Tc-99(m)-TG was injected intravenously in mice bearing MC26 colon carcinoma and tissue samples were analysed by gamma scintillation counting at various times. Uptake of Tc-99(m)-TG in tumour at 1 and 3 h was 1.6 +/- 0.3% and 1.2 +/- 0.3%; the tumour to muscle ratios were 2.7:1 and 4:1 respectively. The autoradiographic biodistribution of Tc-99(m)-TG in MX-1 human breast xenografted nude mice showed more persistent tumour uptake of Tc-99(m)-TG than C-14-2-deoxyglucose (C-14-DG). Tc-99(m)-TG accumulated in the centre of the tumours; C-14-DG was decreased in this central region probably because of zones of infarction on necrosis. The discordance between the tumour uptake of Tc-99(m)-TG and C-14-DG indicates that Tc-99(m)-TG does not act like a glucose analog, suggesting Tc-99(m)-TG avidity for zones of infarction or necrosis. The further study of Tc-99(m)-TG in tumours and ischaemic injury is warranted. ((C) 1999 Lippincott Williams & Wilkins).