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

Abstract

6-[18F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism—its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6-[18F]fluoro-m-tyrosine (FMT), which also targets L-amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol-O-methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. 15 Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high-resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer (http://surfer.nmr.mgh.harvard.edu); region-specific uptake rate constants (Kocc) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional Kocc were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT Kocc were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical Kocc were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD.

Kainic Acid Induces mTORC1-Dependent Expression of Elmo1 in Hippocampal Neurons

“…Because gene profiling only reveals the amount of a transcript, one should consider the role of mTOR in either the regulation of transcription or mRNA stabilization. In nonneuronal cells, mTOR is known to regulate activity, cellular localization, and the level of several transcription factors [16], e.g., hypoxia-inducible factor 1α (HIF-1α), increased expression of which was reported in animal models of epilepsy [65, 66]. However, in our analysis, we did not identify TFBS for HIF-1α in promoters of KA-upregulated genes that were affected by rapamycin.…”

Alterations of Myelin Content in Parkinson’s Disease: A Cross-Sectional Neuroimaging Study

“…Atypical antipsychotics, which antagonize dopamine (D 2 ) and serotonin (5-HT 2 ) receptors [ 57 ] also appear to increase or preserve myelination [ 15 , 58 ]. The regional distribution of dopaminergic radiotracers in the brain is correlated with dopamine receptor levels [ 59 ]. Therefore, it is possible that increased VF M in the thalamus, frontal, and temporal cortices and connections (such as the genu of corups callosum) we observed in this study reflect the effects of anti-Parkinson medications on brain myelin content.…”

Anterior cingulate dopamine turnover and behavior change in Parkinson’s disease

“…We chose to focus this investigation on anterior cingulate cortex in part because K* i in this region is highest of frontal cortical regions (Moore et al 2003; Li et al 2014), and has been related to executive tasks in other studies (Bruck et al 2005). Anterior cingulate cortex is a major target of mesocortical dopaminergic projections arising from the ventral tegmental area (Paus 2001).…”

“…The anterior cingulate cortex, which receives dopaminergic projections from the ventral tegmental area through the mesolimbic pathway, is the region of highest FDOPA uptake amongst frontal cortical regions (Moore et al 2003; Li et al 2014). Dopamine levels in prefrontal cortex are known to influence executive performance in non-PD populations (Meyer-Lindenberg et al 2005).…”