Biodistribution of 3,4-dihydro-5-[C-11]methoxy-1(2H)-isoquinolinone, a potential PET tracer for poly(ADP-ribose) synthetase

Poly(adenosine diphosphate-ribose) synthetase (PARS) is a nuclear enzyme th at is activated by deoxyribonucleic acid (DNA) strand breaks and participat es in DNA repair, Excessive PARS activation, however, leads to cell death d ue to depletion of adenosine triphosphate (ATP). To evaluate whether it is possible to detect excessive activation of PARS with positron emission tomo graphy (PET), we examined the pharmacokinetics of 3,4-dihydro-5-[C-11]metho xy-1(2H)-isoquinolinone ([C-11]MIQO), a potent poly(ADP-ribose) synthetase inhibitor, in the brain of rats and monkeys. Although the uptake of [C-11]M IQO in the brain of normal rats was low, [C-11]MIRO was rapidly incorporate d into and then quickly washed out from the brain. The uptake of the radiot racer in the brain of normal monkeys was also row; however, [C-11]MIQO gave a distribution image that differed from that of cerebral blood flow obtain ed by [O-15]water-PET. No localization of [C-11]MIQO in the brain of normal monkeys was observed. Low accumulation of some radioactivity was also obse rved in muscles surrounding the brain of monkeys, but did not seem to inter fere with measurement of [C-11]MIQO uptake in the brain with PET. Thus, det ection of [C-11]MIQO uptake with PET may be useful for detecting PARS activ ity in ischemic injury. NUCL MED BIOL 27;8:701-705, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.