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• W1965537253 abstract "Longitudinal measurements of dopamine (DA) uptake and turnover in transgenic rodents may be critical when developing disease-modifying therapies for Parkinson's disease (PD). We demonstrate methodology for such measurements using [ 18 F]fluoro-3,4-dihydroxyphenyl- L-alanine ([ 18 F]FDOPA) positron emission tomography (PET). The method was applied to 6-hydroxydopamine lesioned rats, providing the first PET-derived estimates of DA turnover for this species. Control ( n = 4) and unilaterally lesioned ( n = 11) rats were imaged multiple times. Kinetic modeling was performed using extended Patlak, incorporating a k loss term for metabolite washout, and modified Logan methods. Dopaminergic terminal loss was measured via [ 11 C]-(+)-dihydrotetrabenazine (DTBZ) PET. Clear striatal [ 18 F]FDOPA uptake was observed. In the lesioned striatum the effective DA turnover increased, shown by a reduced effective distribution volume ratio ( EDVR) for [ 18 F]FDOPA. Effective distribution volume ratio correlated ( r > 0.9) with the [ 11 C]DTBZ binding potential ( BP ND ). The uptake and trapping rate ( k ref ) decreased after lesioning, but relatively less so than [ 11 C]DTBZ BP ND . For normal controls, striatal estimates were k ref = 0.037 ± 0.005 per minute, EDVR = 1.07 ± 0.22 and k loss = 0.024 ± 0.003 per minute (30 minutes turnover half-time), with repeatability (coefficient of variation) ≤11%. [ 18 F]fluoro-3,4-dihydroxyphenyl- L-alanine PET enables measurements of DA turnover in the rat, which is useful for developing novel therapies for PD." @default.
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• W1965537253 date "2012-08-29" @default.
• W1965537253 modified "2023-10-14" @default.
• W1965537253 title "<i>In-vivo</i> Measurement of LDOPA Uptake, Dopamine Reserve and Turnover in the Rat Brain Using [¹⁸F]FDOPA PET" @default.
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• W1965537253 doi "https://doi.org/10.1038/jcbfm.2012.120" @default.
• W1965537253 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3597374" @default.
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