Synthesis of an (iodovinyl)misonidazole derivative for hypoxia imaging.
Nitroimidazoles undergo a bioreduction in viable hypoxic tissue, resulting in trapping within these tissues, as demonstrated by misonidazole. A radioiodinated analogue of misonidazole (IVM, (E)-5-(2-Nitroimidazolyl)-4-hydroxy-1-iodopent-1-ene, 3) has been synthesized by halodestannylation, for evaluation as an imaging agent for hypoxia. A key step in the synthetic sequence involves the use of the Lewis acid BF3.Et2O to promote the nucleophilic ring opening of glycidyl tosylate with (E)-1-lithio-2-(tributylstannyl)ethylene. Direct comparison of IVM versus F-MISO (2) another misonidazole type hypoxic cell marker, in several in vitro cell culture studies, indicates that IVM behaves in analogous fashion to F-MISO and has promise as a hypoxia imaging agent for SPECT.
Biskupiak
J E
JE
Department of Radiology, University of Washington, Seattle.
Grierson
J R
JR
Rasey
J S
JS
Martin
G V
GV
Krohn
K A
KA
D000818:Animals; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D003412:Cricetulus; D000860:Hypoxia / Q000175:diagnosis; D051379:Mice; D008807:Mice, Inbred BALB C; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship
D011838:Radiation-Sensitizing Agents; C069793:5-(2-nitroimidazolyl)-4-hydroxy-1-iodopent-1-ene; C059168:1-(2-nitro-1-imidazoyl)-3-(2,2,2-trifluoroethoxy)-2-propanol; D008920:Misonidazole