PET 6-[18F]fluoro-L-m-tyrosine studies of dopaminergic function in human and nonhuman primates

Abstract

Although positron emission tomography (PET) and the aromatic L-amino acid decarboxylase (AADC) tracer 6-[18 F]fl uoro-L-m-tyrosine (FMT) has been used to assess the integrity of the presynaptic dopamine system in the brain, relatively little has been published in terms of brain FMT uptake values especially for normal human subjects. Twelve normal volunteer subjects were scanned using PET and FMT to determine the range of normal striatal uptake values using Patlak graphical analysis. For comparison, seven adult rhesus monkeys were studied and the data analyzed in the same way. A subset of monkeys that were treated with a unilateral intracarotid artery infusion of the dopamine neurotoxin MPTP showed an 87% decrease in striatal FMT uptake. These fi ndings support the use of PET and FMT to image AADC distribution in both normal and diseased brains using Patlak graphical analysis and tissue input functions.

Evaluation of 6-11C-Methyl-m-Tyrosine as a PET Probe for Presynaptic Dopaminergic Activity: A Comparison PET Study with β-11C-l-DOPA and 18F-FDOPA in Parkinson Disease Monkeys

“…The plasma metabolic analyses of 11 C-6MemTyr revealed that the inhibitory action of AADC by carbidopa at 5 mg/kg by mouth may be comparable to that determined by its intravenous administration at 0.15 mg/kg, both of which could be too low to affect the brain uptake of 11 C-6MemTyr in the living brain. Taken together, 11 C-6MemTyr should be useful as a PET probe for presynaptic dopamine imaging, because it can provide the sufficiently high Ki values in the striatum of the living brain even without carbidopa, and its MTGA Ki value was as high as that of 18 F-FmT in the monkey brain (22).…”

“…6-18 F-fluoro-L-m-tyrosine ( 18 F-FmT) has been proposed for presynaptic dopamine imaging (20)(21)(22)(23). 18 F-FmT is decarboxylated to 6-18 F-fluoro-m-tyramine ( 18 F-FmTA) by AADC with a 10-foldgreater affinity than 18 F-FDOPA (21).…”

Genetic Variation in the Alpha Synuclein Gene (SNCA) Is Associated With BOLD Response to Alcohol Cues

“…Future work could aim to identify their functional signifi cance, or whether they are in linkage disequilibrium with an SNP in a functional region. Future work also could consider testing effects of genetic variation in human subjects on presynaptic dopamine using 6-[18F]-Fluoro-m-tyrosine positron emission tomography (PET) (Eberling et al, 2007) or 6-[18F]-fl uorodopa (Heinz et al, 2005) PET while also measuring evoked response to alcohol using fMRI.…”

Effect of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys

“…For quantitative analysis of 18 F-BCPP-EF, arterial blood samples were obtained every 8 s until 64 s after tracer injection and then at 90 and 150 s and at 4,6,10,20,30,45,60,75, and 90 min. Blood samples were centrifuged to separate plasma and were weighed, and the radioactivity was measured using a g-counter (1480 Wizard; Perkin Elmer).…”

“…PMOD software was also used to calculate the nondisplaceable binding potential (BP ND ) of 11 C-DASB, 18 F-MPPF, and 11 C-PE2I via a simplified reference tissue model (27), with the time-activity curve in the cerebellum applied as the indirect input function, as well as to perform multiple-time graphical analysis of 11 C-6MemTyr (9,22,23,28,29), with the time-activity curve in the occipital cortex applied as the input function (30).…”