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

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.

Blood flow distribution in necrotic versus nonnecrotic rabbit hearts.

The spatial myocardial blood flow heterogeneity of the normal heart was previously investigated by means of the standard microsphere-defined regional myocardial blood flow in nonischemic hearts. We determined the probability density functions of coronary blood flows in the rabbit heart at selected macroautoradiographic 20-microns cross-sections of the left ventricle in nonischemic as well as infarcted hearts. Macroautoradiography gave us spatial resolutions of 0.1-0.2 mm. As a tracer we used 14C-iodoantipyrine given into the root of the aorta. We report here for the first time a systematic study of the shape of the flow probability density functions during acute regional myocardial necrosis. As the hearts became progressively and extensively necrotic, the distribution of flows changed its characteristics showing two independent components. The first component was the peak representing the nonischemic regions in the hearts subjected to acute ischemia. The second component was a monotonically decreasing component associated with very low flows and necrosis in the severely hypoperfused portion of the hearts. This monotonically decreasing component became larger as the extent of ischemia increased and was well separated from the peak attributable to the nonischemic regions. We could not demonstrate a leftward shift of the nonischemic central peak in the ischemic hearts. Our research shows that in transaxial radionuclide cardiac sections, such as those that might be obtained and analyzed in clinical SPECT and clinical PET, variable amounts of myocardial necrosis will result in a composite curve of myocardial blood flow heterogeneities. One portion of the curve will indicate the distribution of flows in the nonischemic zones. The other portion will vary in magnitude with the extent of ischemia, exhibit the shape of monotonically decreasing curve. Depending upon the spatial resolution of the radionuclide imaging technique utilized, a border zone will exist representing the interface between normally perfused and occluded vascular beds. In our investigation, it was found that the border zone determined statistically was consistently and significantly smaller than the border zone determined visually.