Localization of trapping of 6-[18F]fluoro-L-m-tyrosine, an aromaticL-amino acid decarboxylase tracer for PET

Abstract

The purpose of this study was to address four major questions regarding 6-FMT, a noncatecholic PET tracer for AAAD: 1) Where is the specific uptake of 6-FMT? 2) Why does it accumulate where and to the degree that it does? 3) How does its uptake differ from that of fluoroDOPA globally? and 4) Does its regional uptake differ significantly from that of fluoroDOPA? High-resolution PET scans were obtained in three rhesus monkeys using 6-FMT and in two of them using fluoroDOPA. Anatomic distribution was analyzed visually and quantitative uptake of 6-FMT was compared with published regional decarboxylase activity and monoamine neurotransmitter concentrations. In addition to high uptake in the dopamine-rich striatal nuclei, there was specific uptake of 6-FMT in brain regions which have little dopaminergic innervation but which have other amines in significant concentration. 6-FMT uptake correlated best with regional AAAD activity (r = 0.97). It correlated slightly less well with the sum of catecholamine and indolamine neurotransmitter concentrations, but does not correlate with dopamine concentration. The uptake of 6-FMT is greater than that of fluoroDOPA, with only slight differences in their regional distributions. Radiolabeled analogs of DOPA are often implicitly or explicitly regarded as tracers for presynaptic dopaminergic function. However, localization of these tracers more broadly includes many regions with relatively high concentrations of norepinephrine and serotonin. This may be especially important in diseases or experimental states in which dopaminergic neurons are selectively reduced, and may allow for the study of nondopaminergic neuronal systems in vivo with this tracer.

A dual‐tracer study of extrastriatal 6‐[18F]fluoro‐m‐tyrosine and 6‐[18F]‐fluoro‐l‐dopa Uptake in Parkinson's disease

“…This is one of the first human studies to compare extrastriatal uptake between FMT and FDOPA. As was seen in a similar study of three non-human primates (Brown et al, 1999a), regional uptake rate constants were higher for FMT in regions of high/specific uptake, but similar or indistinguishable between tracers in regions of low uptake. Unfortunately the study design, which did not include control subjects, precludes comment on the relative sensitivity of the two tracers.…”

Noninvasive assessment of aromaticL-amino acid decarboxylase activity in aging rhesus monkey brain in vivo

“…In order to clarify the role of aging in AAAD activity in vivo, we examined the uptake of another L-DOPA analog, 6-fluoro-m-tyrosine (FMT), in the brains of rhesus monkeys of various ages using PET imaging. We previously found FMT to give improved PET images of dopamine terminals in rhesus monkey brains and its CNS uptake correlates very well with AAAD localization (Brown et al, 1999). Furthermore, in vitro and in vivo studies support the notion that FMT uptake, unlike FDOPA, is independent of post-AAAD metabolic steps, which suggests that FMT uptake may provide a better measure of AAAD activity than FDOPA uptake.…”

Validation of midbrain positron emission tomography measures for nigrostriatal neurons in macaques

“…Another tracer of dopamine synthesis, [ 18 F]‐fluorometatyrosine (FMT), also reflects decarboxylase activity but is not subjected to O‐methylation. FMT may not be as specific for dopaminergic neurons as FD . However, PET measures of midbrain uptake of FMT have been done in nonhuman primates and humans .…”