Loss of metabolites from monkey striatum during PET with FDOPA

The decarboxylation of 6-[¹⁸F]fluorodopa (FDOPA) and retention of the product [¹⁸F]fluorodopamine within vesicles of catecholamine fibers results in the labeling of dopamine-rich brain regions during FDOPA/PET studies. However, this metabolic trapping is not irreversible due to the eventual diffusion of [¹⁸F]fluorodopamine metabolites from brain. Consequently, time–radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood–brain clearance of FDOPA (K, ml g⁻¹ min⁻¹) can be corrected for this loss by the elimination rate constant k (min⁻¹). Similarly, the DOPA decarboxylation rate constant (k, min⁻¹) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k (min⁻¹). To compare the two methods, we calculated the two elimination rate constants 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-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K and k in striatum; in the case of k, variance of the 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 estimates of k and k suggests that both rate constants reveal loss of decarboxylated metabolites from brain. Synapse 41:212–218, 2001. © 2001 Wiley-Liss, Inc.