Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10916334 | Nuclear Medicine and Biology | 2005 | 7 Pages |
Abstract
Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury. PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults. A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis. Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions. The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC50=20 nM) and is a suitable lead compound for PET radiotracer development. The synthesis of [11C]PJ34 was accomplished by base-catalyzed reaction of the corresponding des-methyl precursor, N-(5,6-dihydro-6-oxophenanthridin-2-yl)-2-(methylamino)acetamide with [11C]methyl iodide in DMF. The radiolabeling yield was 60% and the specific activity was â¼2000 mCi/μmol (decay corrected to E.O.B.). The total radiosynthesis time was approximately 50 min. Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [11C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated. These data indicate that [11C]PJ34 may be a useful radiotracer for imaging tissues undergoing cellular death via necrosis.
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Authors
Zhude Tu, Wenhua Chu, Jun Zhang, Carmen S. Dence, Michael J. Welch, Robert H. Mach,