Measuring dopaminergic function in the 6-OHDA-lesioned rat: a comparison of PET and microdialysis

作者:Walker Matthew D*; Dinelle Katherine; Kornelsen Rick; Lee Anna; Farrer Matthew J; Stoessl A Jon; Sossi Vesna
来源:EJNMMI Research, 2013, 3(1): UNSP 69.
DOI:10.1186/2191-219X-3-69

摘要

Background: [F-18]fluorodopa (FDOPA) positron emission tomography (PET) allows assessment of levodopa (LDOPA) metabolism and is widely used to study Parkinson's disease. We examined how [F-18]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: [F-18]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 [C-11] dihydrotetrabenazine (DTBZ), which is a ligand for the vesicular monoamine transporter marker and allowed assessment of denervation severity. Results: The 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. Conclusions: The demonstrated strong correlations between the PET and microdialysis measures can aid in the interpretation of [F-18]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.

  • 出版日期2013