Loss of metabolites from monkey striatum during PET with FDOPA

The decarboxylation of 6-[F-18]fluorodopa (FDOPA) and retention of the prod uct [F-18]fluorodopamine within vesicles of catecholamine fibers results in the labeling of dopamine-rich brain regions during FDOPA/PET studies. Howe ver, this metabolic trapping is not irreversible due to the eventual diffus ion of [F-18]fluorodopamine metabolites from brain. Consequently, time-radi oactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K-i(D), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate co nstant k(cl)(Lin) (min(-1)). Similarly,. the DOPA decarboxylation rate cons tant (k(3)(D), min(-1)) calculated by compartmental analysis can also be co rrected for metabolite loss by the elimination rate constant k(9)(DA) (min( -1)). To compare the two methods, we calculated the two elimination rate, c onstants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) lesions. Use of the extended models increased the magnitude s of K-i(D) and k(3)(D) in striatum; in the case of k(3)(D), variance of th e estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual e stimates of k(cl)(Lin) and k(9)(DA) suggests that both rate constants revea l loss of decarboxylated metabolites from brain. Synapse 41:212-218, 2001. (C) 2001 Wiley-Liss, Inc.