Loss of metabolites from monkey striatum during PET with FDOPA.
The decarboxylation of 6-[(18)F]fluorodopa (FDOPA) and retention of the product [(18)F]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 [(18)F]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(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (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(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), 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(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss of decarboxylated metabolites from brain.
Cumming
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PET Center, Arhus Kommunehospital, Arhus, Denmark. paul@pet.auh.dk
Munk
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Doudet
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D000818:Animals; D001812:Blood-Brain Barrier; D003714:Denervation; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D008253:Macaca mulatta; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase; D004298:Dopamine