Kinetics of L-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) in striatum and cerebellum were measured in 10 normal human subjects with positron emission tomography (PET) from 0 to 120 min after an intravenous bolus injection of the tracer. The time course of the arterial plasma concentrations of the tracer and its metabolites was also assayed biochemically. FDOPA compartmental models that are based on biochemical information were investigated for their consistency with the measured striatal and cerebellar tissue kinetics. A modeling approach was also developed for separating plasma FDOPA and metabolite time-activity curves from the measured total 18F time-activity curve in plasma. Results showed that a model consisting of three separate compartments for tissue FDOPA, tissue 6-[18F]fluorodopamine (FDA) and its metabolites, and tissue L-3,4-dihydroxy-6-[18F]fluoro-3-O-methylphenylalanine (3-OMFD) could describe adequately the striatal kinetics in humans. Based on this model, the FDOPA transport constant across the blood-brain barrier (BBB) (K1), the FDOPA decarboxylation rate constant (k3), and the turn-over rate constant of FDA and its metabolites (k4) could be estimated by model fitting to the tissue kinetics and were found for the normal subjects to be 0.031 +/- 0.006 ml/min/g (mean +/- SD), 0.041 +/- 0.015/min, and 0.004 +/- 0.002/min, respectively. About 50% of the FDOPA that crossed the BBB from plasma to striatum was decarboxylated. The decarboxylation constant with respect to plasma FDOPA (K3) was 0.015 +/- 0.003 ml/min/g. The BBB transport corresponded to a permeability-surface area product of 0.032 ml/min/g for FDOPA. For 3-OMFD, the BBB transport was 1.7 times faster. The effects of tissue heterogeneity on the FDOPA kinetics and on the estimated model parameters were also investigated. The usefulness and implications of these findings for interpretation of PET FDOPA studies are discussed.

A modelling approach is developed to generate the full time course of an injected radiotracer and its labelled metabolites in plasma/blood, based on measurements of the total radioactivities in withdrawn plasma/blood samples. A compartmental model is used to describe the conversion of an injected tracer to its metabolites in the body. The model equation is formulated with the total radioactivity concentration curve as the input function. The utility and characteristics of the approach in quantitative positron emission tomographic (PET) studies are shown with two examples. In the first example, using the tracer 6-[18F]fluoro-L-dopa (FDOPA), the approach is shown to derive the full time course of plasma FDOPA and its metabolites. In the second example of dynamic 15O oxygen PET, the approach is used to solve a deconvolution problem to give separated time-activity curves of 15O oxygen and 15O water in blood. The modelling approach improves the separation of blood/plasma time-activity curves and leads to better quantitative interpretation of PET results.

6-[18F]Fluoro-L-DOPA (FDOPA) cerebral kinetics and metabolism were correlated in normal primates (Macaca nemestrina) and primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced unilateral Parkinsonism. Application of a tracer kinetic model to positron emission tomography (PET) data indicated that the model allows reliable estimation of FDOPA blood brain barrier transport, decarboxylation and release of stored 6-[18F]fluorodopamine (FDA) radioactivity in normal striatum (k4 = 0.005/min, turnover half-time greater than or equal to 2 hr), in agreement with biochemical data. PET scans of MPTP treated monkeys revealed 40-50% reduction in total striatal activity in comparison with pre-MPTP scans. Monkey brain biochemical analysis revealed that the reduction in activity was mainly due to a decrease in FDA and its metabolites, 6[18F]fluorohomovanillic (FHVA) and 6-[18F]fluoro-3, 4-dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3-0-methyl-6-[18F]fluoro-L-DOPA (3-OMFD) of peripheral origin. The (FHVA + FDOPAC)/FDA ratio was 1:2 in normal putamen and greater than or equal to 6:1 in the lesioned putamen, indicative of a dramatic increase in turnover of FDA. Both kinetic and biochemical data indicate that FDOPA labels a slow turnover rate pool of dopamine in rat and primate brain. This turnover rate for stored dopamine (DA) is accelerated with dopaminergic cell losses (e.g., MPTP-induced Parkinsonism).

Summary:In this work, we introduce 6-['sFlfluoro-L-m tyrosine (6-FMT) and compare its in-vivo kinetic and bio chemical behaviors in monkeys and rodents with those of 4-FMT and 6-['sFlfluoro-L-3,4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3-0-methylation, offer a nonpharmacologicai alternative to the use of catechol-O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essen tially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and ro dents, these new radiofluorinated m-tyrosine analogs ac cumulate selectively in striatal structures and allow for

Fragrances have rapid effect on our central nervous system, such as making the spirit of relaxation, relieving tensions and refreshing ourselves. However, the release of fragrances is not stable. Here, we added photo-driven mesoporous silica nanocolumns loaded with sandela 803 (MS-C@S803) into wallpaper to obtain fragrant wallpaper (MS-C-W@S803). We then analysed the effects of MS-C-W@S803 and pure sandela 803 treated wallpaper (W@S803) on the CNS of mice and explored the internal mechanism of these effects. Besides, we evaluated the short-term (7 days) and long-term (30 days) effects of the fragrance treated wallpaper. In behaviouristics level, we detected the anxiolytic effects via elevated plus maze and open field test. In tissue level, we analysed the neural activity in hippocampus, hypothalamus and olfactory bulb regions via measuring the electrophysiological signal. In cell level, we tested the nerve regeneration in hippocampus, substantia nigra and corpus striatum via immunofluorescence staining with the anti-BrdU antibody. In molecule level, we measured the expression of dopamine, acetylcholine, γ-aminobutyric acid (GABA) and N-methyl-D-aspartic acid (NMDA) via liquid chromatography-mass spectrometry. Finally, we find that MS-C-W@S803 had anxiolytic effects on the CNS of mice, and the effects were more significant as time progresses.