Radioiodinated 2-nitrobenzyl carbamates as bioreductive alkylating agents for tissue hypoxia.
Three N-methylcarbamates of iodonitrobenzyl alcohols (4-iodo-2-nitrobenzyl alcohol 2, 5-iodo-2-nitrobenzyl alcohol 3 and 4-iodo-2,6-dinitrobenzyl alcohol 4) bearing [125I] have been prepared and characterized for their lipophilicity, their reduction potentials and the in vivo liability of the radioiodine in healthy mice. Based upon these results, 2 and 4 were tested in tumour-bearing mice showing limited uptake of radioactivity in tumours and a tumour-to-blood ratio of less than 1. Consequently these particular carbamates are not satisfactory as hypoxia imaging agents.
Department of Chemistry, University of Western Ontario, London, Canada.
P A
PA
Culbert
A V
AV
Wearring
M J
MJ
Chamberlain
D H
DH
Hunter
D000477:Alkylating Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002219:Carbamates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000528:radiation effects*; D004563:Electrochemistry; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000532:radiotherapy; D009578:Nitrobenzenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010084:Oxidation-Reduction; D014018:Tissue Distribution
D000477:Alkylating Agents; D002219:Carbamates; D007457:Iodine Radioisotopes; D009578:Nitrobenzenes