[18F]FMT; Parkinson's disease; preclinical imaging; dopaminergic dysfunction; rat model
Abstract :
[en] Objectives: Rat models of Parkinson’s disease (PD), such as lesioned rats with 6-hydroxydopamine (6-OHDA), are useful for studying dopamine (DA)-related functions. 6-18F-fluoro-m-tyrosine (6-18F-FMT) is an effective PET tracer to evaluate of DA terminals integrity and L-aromatic amino acid decarboxylase (AAAD) metabolic pathway. However, there are currently no available quantitative PET studies using 18F-FMT in 6-OHDA lesioned rats. In this context, we investigated the feasibility of in vivo PET study using 18F-FMT on 6-OHDA PD’s model.
Methods: 10 µg of 6-OHDA were injected into the right medial forebrain bundle (MFB) of male Sprague-Dawley rats (n=8). As control, sham-treated rats (n=8) were injected with vehicle only but otherwise treated identically. Striatal DA presynaptic activity was assessed by dynamic 18F-FMT-PET. Structural T2-weighted brain images were acquired on a 9.4T MRI and were used for co-registration. After normalization on a MRI template, kinetic analysis was performed by “Patlak Reference” model, using PMOD software.
Results: Striatal accumulation of 18F-FMT was observed in rats pretreated with benserazide, a peripheral AAAD inhibitor. As consequence of the 6-OHDA-lesion, significant decrease of 18F-FMT accumulation was recorded in the striatum ipsilateral to the lesion. Lesioned rats had dramatically reduced uptake constant Ki in the ipsilateral striatum compared to the contralateral striatum (p<0.001) and to the ipsilateral striatum of sham-treated rats (p<0.005). The Ki ratio (Ipsi./Contra.) was equivalent to 94% in the sham group and dropped to 41% in the lesioned group.
Conclusions: 18F-FMT PET enables us to quantify loss of DA presynaptic function in unilaterally 6-OHDA lesioned rats. These results encourage us to pursue further investigations in a longitudinal way and to monitor the progression of the dopaminergic dysfunction in more moderate and gradual preclinical PD models.
Research Center/Unit :
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
Michel, Anne
Hustadt, F
Garraux, Gaëtan ; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie du système nerveux
Lemaire, Christian ; Université de Liège > Centre de recherches du cyclotron
Plenevaux, Alain ; Université de Liège > Centre de recherches du cyclotron
Language :
English
Title :
18F-FMT: a reliable PET tracer for in vivo evaluation of dopaminergic dysfunction in Parkinson’s Disease rat model.
