COMBINED FDOPA AND 30MFD PET STUDIES IN PARKINSONS-DISEASE

PET has been used to quantify striatal 6-[F-18]fluoro-L-dopa (FDOPA) u ptake as a measure of presynaptic dopaminergic function. It has been s uggested that the estimation of dopa-decarboxylation (DDC) rate, k(3)( D), using a compartmental approach to dynamic FDOPA/PET data, can prov ide a better objective marker of parkinsonism. This modeling process, however, requires many assumptions to estimate DDC activity with accep table errors. Methods: We combined FDOPA 3-O-methyl-fluorodopa PET stu dies on three normal subjects and five Parkinson's disease patients. R esults: The contradicted modeling assumptions are: (a) the rate consta nts across the blood-brain barrier, K-1(D) and k(2)(D), for 3OMFD and FDOPA were in similar range (ratio congruent to 1) and thus not equal to assumed values of K-1(M)/K-1(D) of 2.3 derived from rat studies and applied to human FDOPA studies and (b) the K-1(D)/k(2)(D) ratio for f rontal cortex was not equal to that for the striatum (0.70 +/- 0.15 ve rsus 1.07 +/- 0.3; p < 0.002). Discriminant analyses indicate that sim ple estimates like the striatum-to-occipital ratio, or the graphically derived unidirectional transport rate constant (K-1(FD)) Separate nor mals from Parkinson's disease patients at least as accurately as estim ates of striatal DDC activity (k(3)(D)). Conclusion: Measurements of s triatal DDC activity with dynamic FDOPA/PET and compartmental modeling may be based on incorrect assumptions. Even though such complex model s yield microparameters that may be applicable to certain clinical res earch demands, they may produce misleading results in other experiment al settings.