Abstract
Although positron emission tomography (PET) and the aromatic L-amino acid decarboxylase (AADC) tracer 6-[18F]fluoro-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 findings 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.
Highlights
Positron emission tomography (PET) has been used extensively to study the activity of aromatic L-amino acid decarboxylase (AADC) in the brains of both human and nonhuman primates
While FDOPA is well validated as a dopaminergic tracer (Eidelberg et al, 1994; Pate et al, 1993; Vingerhoets et al, 1994), it has the disadvantage of being subject to peripheral metabolism by catechol-O-methyltransferase (COMT)
Kic values decreased significantly following unilateral MPTP treatment in monkeys (t = 13.46, p < 0.001), with reductions of 87% in the treated hemisphere
Summary
Positron emission tomography (PET) has been used extensively to study the activity of aromatic L-amino acid decarboxylase (AADC) in the brains of both human and nonhuman primates. An alternative AADC tracer, 6-[18F]fluoro-L-m-tyrosine (FMT), is not subject to O-methylation resulting in better quality images with higher signal to noise and more straightforward kinetics (DeJesus et al, 1997; Jordan et al, 1997; Nahmias et al, 1995). We have used FMT extensively in the study of both normal and parkinsonian monkeys treated with the dopamine neurotoxin MPTP (Bankiewicz et al, 2006a,b; Eberling et al, 1997, 1998a, 2000, 2003; Forsayeth et al, 2006; Jordan et al, 1997) and have recently begun PET-FMT studies in normal human subjects and patients with Parkinson’s disease (PD). We compared FMT uptake in monkeys before and after MPTP treatment as an animal model of PD in order to evaluate the use of this approach in an established disease model
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