Molecular Imaging of PDE10A Knockout Mice with a Novel PET Radiotracer: [(11)C]T-773
| Autor: | Nahid Amini, Balázs Gulyás, Shotaro Miura, Akihiro Takano, Haruhide Kimura, Takahiko Taniguchi, Jenny Häggkvist, Miklós Tóth, Christer Halldin, Vladimir Stepanov, Ryuji Nakao |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Pathology Neuroimaging Striatum Biology Medium spiny neuron Mice Internal medicine medicine Radioligand Animals Radiology Nuclear Medicine and imaging Carbon Radioisotopes Radioactive Tracers Brain Chemistry Mice Knockout Phosphoric Diester Hydrolases Wild type Phosphodiesterase Brain Ligand (biochemistry) Molecular Imaging Endocrinology Oncology Positron-Emission Tomography Knockout mouse PDE10A |
| Zdroj: | Molecular imaging and biology. 17(4) |
| ISSN: | 1860-2002 |
| Popis: | [(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.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.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 0.0001). The striatal BPND values (mean ± SD) were 0.0 ± 0.0 (HOM), 0.14 ± 0.07 (HET) and 0.56 ± 0.15 (WILD). The BPND values were significantly lower in homozygous and heterozygous animals compared to wild type (p 0.0001).The novel PDE10A radioligand [(11)C]T-773 shows increased signals with higher levels of PDE10A and acceptable binding in the striatum in control animals compared to knockout mice. |
| Databáze: | OpenAIRE |
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