| Autor: |
Becker, Guillaume, Bahri, Mohamed Ali, Michel, Anne, Hustadt, Fabian, Garraux, Gaëtan, Luxen, André, Lemaire, Christian, Plenevaux, Alain |
| Předmět: |
|
| Zdroj: |
Journal of Neurochemistry; May2017, Vol. 141 Issue 4, p626-635, 10p |
| Abstrakt: |
Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson's disease ( PD), in vivo quantitative imaging of dopamine ( DA) containing neurons in animal models of PD is of critical importance in the preclinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography ( PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6- OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [18F]fluoro-3,4-dihydroxyphenyl- L-alanine ([18F] FDOPA) and 6-[18F]fluoro- L-m-tyrosine ([18F] FMT). Because the imaging signal is theoretically less contaminated by metabolites, we hypothesized that the latter would show stronger relationship with behavioural and post-mortem measures of striatal dopaminergic deficiency. We used a within-subject design to measure striatal [18F] FMT and [18F] FDOPA uptake in eight partially lesioned, eight fully lesioned and ten sham-treated rats. Animals were pretreated with an L-aromatic amino acid decarboxylase inhibitor. A catechol- O-methyl transferase inhibitor was also given before [18F] FDOPA PET. Quantitative estimates of striatal uptake were computed using conventional graphical Patlak method. Striatal dopaminergic deficiencies were measured with apomorphine-induced rotations and post-mortem striatal DA content. We observed a strong relationship between [18F] FMT and [18F] FDOPA estimates of decreased uptake in the denervated striatum using the tissue-derived uptake rate constant Kc. However, only [18F] FMT Kc succeeded to discriminate between the partial and the full 6- OHDA lesion and correlated well with the post-mortem striatal DA content. This study indicates that the [18F] FMT could be more sensitive, with respect of [18F] FDOPA, to investigate DA terminals loss in 6- OHDA rats, and open the way to in vivo L-aromatic amino acid decarboxylase activity targeting in future investigations on progressive PD models. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text