[ carbonyl - 11 C]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ 11 C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain
| Autor: | Robert L. Gladding, Alicia E. Woock, Shuiyu Lu, Jeih-San Liow, Rong Xu, Sami S. Zoghbi, Victor W. Pike, Kimberly J. Jenko, Jinsoo Hong, Robert B. Innis |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Stereochemistry Drug Evaluation Preclinical Receptors Metabotropic Glutamate Article chemistry.chemical_compound Image Processing Computer-Assisted medicine Radioligand Animals Radiology Nuclear Medicine and imaging Carbon Radioisotopes Benzamide Receptor Radiochemistry Radiosynthesis Glutamate receptor Brain Macaca mulatta Cortex (botany) Thiazoles Metabotropic receptor chemistry Positron-Emission Tomography Benzamides Molecular Medicine Metabotropic glutamate receptor 1 Radiopharmaceuticals |
| Zdroj: | Nuclear Medicine and Biology. 42:967-974 |
| ISSN: | 0969-8051 |
| Popis: | Introduction Metabotropic glutamate subtype receptor 1 (mGluR1) is implicated in several neuropsychiatric disorders and is a target for drug development. [ 18 F]FIMX ([ 18 F]4-fluoro-- N -methyl- N --(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide) is an effective radioligand for imaging brain mGluR1 with PET. A similarly effective radioligand with a shorter half-life would usefully allow PET studies of mGluR1 at baseline and after pharmacological or other challenge on the same day. Here we describe the preparation of [ 11 C]FIMX for evaluation in monkey with PET. Methods [ 11 C]FIMX was prepared via Pd-promoted carbonylation of 1-fluoro-4-iodobenzene with [ 11 C]carbon monoxide, aminolysis of the [ 11 C]acyl-palladium complex with the requisite Boc-protected amine, and deprotection with HCl in THF. PET scans of [ 11 C]FIMX injected into a monkey were performed at baseline and after preblock of mGluR1 with measurement of the arterial input function. Results The radiosynthesis required 42min and gave [ 11 C]FIMX in about 5% overall decay-corrected radiochemical yield and with a specific activity of about 100GBq/μmol. PET in rhesus monkey at baseline showed that radioactivity peaked high in receptor-rich cerebellum and much lower in receptor-poor occipital cortex. Radioactivity in cerebellum declined to 32% of peak at 85min. V T at baseline appeared stable in all brain regions after 60min. Under mGluR1 pre-blocked condition, radioactivity uptake in all regions declined more rapidly to a low level. Receptor pre-block reduced V T from 13.0 to 1.5 in cerebellum and from 2.9 to 1.4 in occipital cortex. Conclusion [ 11 C]FIMX is an effective radioligand for imaging mGluR1 in monkey with PET. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect