Positron Emission Tomography Imaging Evaluation of a Novel 18F-Labeled Sigma-1 Receptor Radioligand in Cynomolgus Monkeys
| Autor: | Hongmei Jia, Yingfang He, Shu-fei Lin, Jim Ropchan, Anupama Shirali, Evan Baum, Yiyun Huang, Michael Kapinos, Zhengxin Cai, Hong Gao, Daniel Holden, Songye Li |
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| Rok vydání: | 2020 |
| Předmět: |
Agonist
0303 health sciences Sigma-1 receptor medicine.diagnostic_test Physiology medicine.drug_class Chemistry Cognitive Neuroscience Radiosynthesis Binding potential Cell Biology General Medicine Biochemistry 03 medical and health sciences 0302 clinical medicine In vivo Positron emission tomography Radioligand medicine Biophysics Receptor 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | ACS Chemical Neuroscience. 11:1673-1681 |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.0c00171 |
| Popis: | We report a convenient radiosynthesis and the first positron emission tomography (PET) imaging evaluation of [18F]FBFP as a potent sigma-1 (σ1) receptor radioligand with advantageous characteristics. [18F]FBFP was synthesized in one step from an iodonium ylide precursor. In cynomolgus monkeys, [18F]FBFP displayed high brain uptake and suitable tissue kinetics for quantitative analysis. It exhibited heterogeneous distribution with higher regional volume of distribution (VT) values in the amygdala, hippocampus, insula, and frontal cortex. Pretreatment with the σ1 receptor agonist SA4503 (0.5 mg/kg) significantly reduced radioligand uptake in the monkey brain (>95%), indicating high binding specificity of [18F]FBFP in vivo. Compared with (S)-[18F]fluspidine, [18F]FBFP possessed higher regional nondisplaceable binding potential (BPND) values across the brain regions. These findings demonstrate that [18F]FBFP is a highly promising PET radioligand for imaging and quantification of σ1 receptors in humans. |
| Databáze: | OpenAIRE |
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