Comparative assessment of 6-[18F]fluoro-L-m-tyrosine and 6-[18F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson’s disease rat model.
[en] 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 pre-clinical 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 (AADC) 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 AADC activity targeting in future investigations on progressive PD models.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
Becker, Guillaume ; Université de Liège > Centre de recherches du cyclotron
Bahri, Mohamed Ali ; Université de Liège > Centre de Recherches du Cyclotron > Centre de Recherches du Cyclotron
Michel, Anne; UCB-Pharma
Hustadt, Fabian; UCB-Pharma
Garraux, Gaëtan ; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie du système nerveux
Luxen, André ; Université de Liège > Département de chimie (sciences) > Laboratoire de chimie organique de synthèse
Lemaire, Christian ; Université de Liège > Centre de recherches du cyclotron
Plenevaux, Alain ; Université de Liège > Département de chimie (sciences) > Département de chimie (sciences)
Language :
English
Title :
Comparative assessment of 6-[18F]fluoro-L-m-tyrosine and 6-[18F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson’s disease rat model.
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