Abstract
Background[18 F]fluorodopa (FDOPA) positron emission tomography (PET) allows assessment of levodopa (LDOPA) metabolism and is widely used to study Parkinson's disease. We examined how [18 F]FDOPA PET-derived kinetic parameters relate the dopamine (DA) and DA metabolite content of extracellular fluid measured by microdialysis to aid in the interpretation of data from both techniques.Methods[18 F]FDOPA PET imaging and microdialysis measurements were performed in unilaterally 6-hydroxydopamine-lesioned rats (n = 8) and normal control rats (n = 3). Microdialysis testing included baseline measurements and measurements following acute administration of LDOPA. PET imaging was also performed using [11C]dihydrotetrabenazine (DTBZ), which is a ligand for the vesicular monoamine transporter marker and allowed assessment of denervation severity.ResultsThe different methods provided highly correlated data. Lesioned rats had reduced DA metabolite concentrations ipsilateral to the lesion (p < 0.05 compared to controls), with the concentration being correlated with FDOPA's effective distribution volume ratio (EDVR; r = 0.86, p < 0.01) and DTBZ's binding potential (BPND; r = 0.89, p < 0.01). The DA metabolite concentration in the contralateral striatum of severely (>80%) lesioned rats was lower (p < 0.05) than that of less severely lesioned rats (<80%) and was correlated with the ipsilateral PET measures (r = 0.89, p < 0.01 for BPND) but not with the contralateral PET measures. EDVR and BPND in the contralateral striatum were not different from controls and were not correlated with the denervation severity.ConclusionsThe demonstrated strong correlations between the PET and microdialysis measures can aid in the interpretation of [18 F]FDOPA-derived kinetic parameters and help compare results from different studies. The contralateral striatum was affected by the lesioning and so cannot always serve as an unaffected control.
Highlights
For three decades, [18 F]fluoro-3,4-dihydroxyphenyl-Lalanine ([18 F]FDOPA) positron emission tomography (PET) has served as an imaging biomarker for dopamine (DA) synthesis, storage, and turnover in the human brain [1,2,3,4,5,6]
For microdialysis measures, the concentration of dihydroxyphenylacetic acid (DOPAC) was highly correlated with the concentration of homovanillic acid (HVA) (r = 0.83, p < 0.01) across all rats, with a relationship not significantly different from direct proportionality
The DA metabolite concentration measured contralateral to the lesion in the
Summary
For three decades, [18 F]fluoro-3,4-dihydroxyphenyl-Lalanine ([18 F]FDOPA) positron emission tomography (PET) has served as an imaging biomarker for dopamine (DA) synthesis, storage, and turnover in the human brain [1,2,3,4,5,6]. The increasing availability of the vesicular monoamine transporter 2 (VMAT2). The insertion of dialysis probes directly into the rodent brain provides a means of sampling extracellular fluid (ECF) which can be assayed for various compounds, including its dopamine and dopamine metabolite content. The direct sampling of ECF and the quantification of DA and DA metabolite concentrations within such samples is a commonly available and well-used technique for in vivo research, but the method is invasive and not well suited to longitudinal investigations [13,14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
