title: Accumulation of technetium-99m glucarate: in vitro cell cultures and in vivo tumour models.
abstract: 99mTc-glucarate is an investigational radiopharmaceutical which has been shown to accumulate in acute cerebral and myocardial injuries and in some tumours. In the present work, a survey of possible factors affecting the cellular accumulation of 99mTc-glucarate was carried out in cell lines and strains in vitro and in murine tumours in vivo. Accumulation was enhanced under hypoxic conditions in 12 of the 16 human and murine cell lines and strains studied, and inhibited in the presence of nitroimidazoles. At temperatures lower than 37 degrees C, accumulation was reduced, but a hypoxic/aerobic differential was maintained. Aerobic accumulation of 99mTc-glucarate was enhanced by cyanide. In transplanted tumours in mice, 99mTc-glucarate showed high tumour/muscle and tumour/blood ratios at early times after injection. Pharmacological enhancement of the extent of hypoxia by the administration of hydralazine or nitro-L-arginine resulted in significantly increased accumulation of 99mTc-glucarate in the tumour. The in vitro and in vivo properties of 99mTc-glucarate suggest that it may be useful for tumour imaging in the clinic, although the exact mechanism(s) by which it localizes in tumours remains unknown.
authors.affiliation: Department of Nuclear Medicine, Ontario Cancer Institute, Toronto, Ontario, Canada. jim.ballinger@addenbrookes.nhs.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Ballinger
authors.forename: V
authors.initials: V
authors.lastname: Hsue
authors.forename: A M
authors.initials: AM
authors.lastname: Rauth
mesh_terms: D000818:Animals; D001386:Azides / Q000494:pharmacology; D016466:CHO Cells; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005354:Fibrosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000494:pharmacology; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010100:Oxygen / Q000378:metabolism; D011190:Potassium Cyanide / Q000494:pharmacology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D001386:Azides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C067171:technetium Tc 99m glucarate; D008795:Metronidazole; D005632:Fructose; D008920:Misonidazole; D011190:Potassium Cyanide; D005937:Glucaric Acid; D010100:Oxygen