| Abstract
| - 8-Carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (temozolomide, 1) is an anticancer prodrug. As part of investigations to probe its postulated mode of action using PET wehave developed two rapid radiosynthetic routes for the preparation of temozolomide labeledwith the short-lived positron emitter, carbon-11 (t1/2 = 20.4 min). Reaction of 5-diazoimidazole-4-carboxamide (7) with the novel labeling agent [11C-methyl]methyl isocyanate (8) gave [3-N-11C-methyl]temozolomide (9) in 14−20% radiochemical yield from [11C-methyl]methyl isocyanate(8) (decay corrected). The position of radiolabeling in the 3-N-methyl group was confirmed by[11/13C]colabeling and subsequent carbon-13 NMR spectroscopy. Similarly, the reaction of5-diazoimidazole-4-carboxamide (7) with [11C-carbonyl]methyl isocyanate (10) gave [4-11C-carbonyl]temozolomide (11) in 10−15% radiochemical yield from [11C-carbonyl]methyl isocyanate(10) (decay corrected). Apyrogenic samples of [3-N-11C-methyl]temozolomide (9) and [4-11C-carbonyl]temozolomide (11), with good chemical and radiochemical purities, have been preparedand used in human PET studies.
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