Equilibrium modeling of 5-ht2a receptors with [18f]deuteroaltanserin and pet: feasibility of a constant infusion paradigm

Poly(adenosine diphosphate-ribose) synthetase (PARS) is a nuclear enzyme that is activated by deoxyribonucleic acid (DNA) strand breaks and participates in DNA repair. Excessive PARS activation, however, leads to cell death due to depletion of adenosine triphosphate (ATP). To evaluate whether it is possible to detect excessive activation of PARS with positron emission tomography (PET), we examined the pharmacokinetics of 3,4-dihydro-5[11C]methoxy-1(2H)-isoquinolinone ([11C]MIQO), a potent poly(ADP-ribose) synthetase inhibitor, in the brain of rats and monkeys. Although the uptake of [11C]MIQO in the brain of normal rats was low, [11C]MIQO was rapidly incorporated into and then quickly washed out from the brain. The uptake of the radiotracer in the brain of normal monkeys was also low; however, [11C]MIQO gave a distribution image that differed from that of cerebral blood flow obtained by [15O]water-PET. No localization of [11C]MIQO in the brain of normal monkeys was observed. Low accumulation of some radioactivity was also observed in muscles surrounding the brain of monkeys, but did not seem to interfere with measurement of [11C] MIQO uptake in the brain with PET. Thus, detection of [11C]MIQO uptake with PET may be useful for detecting PARS activity in ischemic injury.