Molecular Imaging of PDE10A Knockout Mice with a Novel PET Radiotracer: [11C]T-773

Purpose [ 11 C]T-773 is a new radioligand for positron emission tomography (PET) targeting the phosphodiesterase 10A enzyme (PDE10A). PDE10A is highly expressed in the striatum by medium spiny neurons, and it has been demonstrated to be involved in the regulation of striatal signaling through the re...

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Bibliographic Details
Published in:Molecular imaging and biology 2015-08, Vol.17 (4), p.445-449
Main Authors: Tóth, Miklós, Häggkvist, Jenny, Stepanov, Vladimir, Takano, Akihiro, Nakao, Ryuji, Amini, Nahid, Miura, Shotaro, Kimura, Haruhide, Taniguchi, Takahiko, Gulyás, Balázs, Halldin, Christer
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Brain Chemistry
Brief Article
Carbon Radioisotopes - chemistry
Carbon Radioisotopes - pharmacokinetics
Imaging
Male
Medicin och hälsovetenskap
Medicine
Medicine & Public Health
Mice
Mice, Knockout
Molecular Imaging - methods
Neuroimaging - methods
Phosphoric Diester Hydrolases - genetics
Positron-Emission Tomography - methods
Radioactive Tracers
Radiology
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Summary:Purpose [ 11 C]T-773 is a new radioligand for positron emission tomography (PET) targeting the phosphodiesterase 10A enzyme (PDE10A). PDE10A is highly expressed in the striatum by medium spiny neurons, and it has been demonstrated to be involved in the regulation of striatal signaling through the reduction of medium spiny neuronal sensitivity towards glutamatergic excitation. PDE10A is associated with Parkinson’s disease and different neuropsychiatric disorders such as Huntington’s disease, obsessive-compulsive disorders (OCD) and schizophrenia. Studies have indicated that the inhibition of PDE10A may represent a novel therapeutic approach to the treatment of the aforementioned diseases characterized by the reduced activity of medium spiny neurons. An appropriate PET radioligand for PDE10A would help to facilitate drug development and drug evaluation. Procedures We have evaluated the [ 11 C]T-773 ligand in PDE10A knockout mice (heterozygous [HET] and homozygous [HOM]) as well as in normal control animals (WILD) with PET. Results The regional percent standardized uptake values (%SUV; mean ± SD) in the striatum were 48.2 ± 1.0 (HOM), 63.6 ± 5.3 (HET) and 85.1 ± 6.3 (WILD). Between each animal group the striatal %SUV values were significantly different ( p  
ISSN:1536-1632
1860-2002
1860-2002
DOI:10.1007/s11307-015-0822-z