In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease

Abstract

Results-PET image analysis showed varying levels of SERT binding reduction (rat #1 = −11%, rat #2 = −4%, rat #3 = −43%; n = 2) and a clear and definitive loss of VMAT2 binding (rat #1 = −87%, rat #2 = −72%, and rat #3 = −91%; n = 1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (PCA, p-chloroamphetamine) showed a significant reduction of uptake in the cortex and hypothalamus regions of the brain. Conclusion-The

Serotonin and molecular neuroimaging in humans using PET

“…Clinical studies have suggested 5-HT 7 receptor's antagonists to act as a treatment option in depression and mood disorders (Mnie-Filali et al 2011), OCD (Hedlund and Sutcliffe 2007) as well as anxiety disorders (Wesolowska et al 2006). The receptor has also been linked to migraine (Wang et al 2010b), pain (Leopoldo et al 2011) and irritable bowel syndrome (Zou et al 2007).…”

“…Other studies suggested SERT to be implicated in OCD (Hesse et al 2011;Simpson et al 2003) and substance abuse (Brown et al 2007), especially MDMA (McCann et al 2005Selvaraj et al 2009). SERT has further been linked to obesity and Parkinson's disease (e.g., Wang et al 2010a).…”

Effect of a chronic treatment with an mGlu5 receptor antagonist on brain serotonin markers in parkinsonian monkeys

“…In addition, a decrease of SERT levels was found in the striatum of PD patients in both post-mortem tissues (Cash et al, 1985;Chinaglia et al, 1993) and living humans (Kerenyi et al, 2003;Roselli et al, 2010). Moreover, positron emission tomography image analysis showed varying levels of SERT binding reduction in the left lesioned side of the striatum when compared to the right non-lesioned side of the striatum in 6-hydroxydopamine (6-OHDA)-lesioned rat PD model (Wang et al, 2010). However, a study using post-mortem brains of PD patients measured a significant decrease of SERT levels only in the caudate nucleus and not in the putamen, while no difference in SERT levels was observed between PD patients with or without LID (Kish et al, 2008).…”

“…SERT is responsible for the recycling/clearance of 5-HT in the brain and SERT levels are also reported to change in PD (Samadi et al, 2007). Moreover, this transporter has been used as a marker for examining 5-HT neuron integrity due to SERT's location on 5-HT neurons (Wang et al, 2010). In addition, a decrease of SERT levels was found in the striatum of PD patients in both post-mortem tissues (Cash et al, 1985;Chinaglia et al, 1993) and living humans (Kerenyi et al, 2003;Roselli et al, 2010).…”

Statistical parametric maps of 18F-FDG PET and 3-D autoradiography in the rat brain: a cross-validation study

“…However, autoradiography requires the sacrifice of the animal, thus negating its use in longitudinal studies. These differences between in vivo small animal PET and autoradiography are widely known, and several studies have compared the results of these two techniques in detail [12][13][14][15][16]. Autoradiography is inherently a two-dimensional (2D) sampling method in which slices are obtained independently without correspondence between neighboring slices.…”