BMS181321 accumulation in rodent and human cells: the role of P-glycoprotein.
A 2-nitroimidazole with a side chain that contains technetium-99m as a chelate, BMS181321, is undergoing evaluation as an imaging agent for myocardial and cerebral ischaemia, as well as a diagnostic probe for hypoxic cells in solid tumours. Its accumulation in hypoxic and aerobic populations of three lines of Chinese hamster ovary cells of differing P-glycoprotein status, as well as one rat and two human cell lines has been determined. There was selective accumulation of BMS181321 in hypoxic vs aerobic cells. P-glycoprotein level was not a factor in this accumulation and hypoxic human cells accumulated BMS181321 more rapidly than the rodent cells. These results indicate P-glycoprotein levels in tumour cells will not confound the use of BMS181321 as a hypoxic cell marker.
Cowan
D S
DS
Department of Medical Biophysics, University of Toronto, Canada.
Melo
T
T
Park
L
L
Ballinger
J R
JR
Rauth
A M
AM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D015687:Cell Hypoxia; D006224:Cricetinae; D004351:Drug Resistance; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D051381:Rats
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; C082027:BMS 181321