[18F]FMT; Parkinson's disease; preclinical imaging; rat model; dopaminergic dysfunction; [18F]DOPA
Abstract :
[en] Background: 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, 30 min after benserazide pretreatment. 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 :
Seret, Alain ; Université de Liège > Département de physique > Imagerie médicale expérimentale
Becker, Guillaume ; Université de Liège > Centre de recherches du cyclotron
Bahri, Mohamed Ali ; Université de Liège > Centre de recherches du cyclotron
Michel, A
Hustadt, F
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 > 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.
Publication date :
09 May 2015
Number of pages :
A0
Event name :
17th Symposium of the Belgian Society of Nuclear Medicine
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.