Triazole-Based Radioligands for PET of P2X7R: Syntheses, Conformational Studies, and Preliminary Autoradiographic Evaluation of [18F]AM-10

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389005%3A_____%2F25%3A00638309" target="_blank" >RIV/61389005:_____/25:00638309 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/25:73631714 RIV/60461373:22330/25:43932318 RIV/60461373:22340/25:43932318 RIV/00098892:_____/25:10159400
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acsomega.5c04531" target="_blank" >https://pubs.acs.org/doi/10.1021/acsomega.5c04531</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsomega.5c04531" target="_blank" >10.1021/acsomega.5c04531</a>

Result language
angličtina
Original language name
Triazole-Based Radioligands for PET of P2X7R: Syntheses, Conformational Studies, and Preliminary Autoradiographic Evaluation of [18F]AM-10
Original language description
The P2X7 receptor is an emerging target for molecular imaging of inflammation in the brain and peripheral tissues. In this work, we focus on five triazole-based ligands with high affinity and selectivity for P2X7 receptors (JNJ-64413739, JNJ-55308942, AM-10, AM-12, and AM-15), which are amenable to autoradiography and positron emission tomography (PET) imaging. We studied the phenomenon of conformational and rotational changes of these molecules by NMR and ab initio calculations. The reaction of ligands AM-10 and AM-12 with [18F]fluoride resulted in an isotopic exchange on the pyrimidine ring, leaving the halogen atoms on the acyl moieties intact. The reaction yielded [18F]AM-10 with a radiochemical yield as high as 27% and a molar activity as high as 152 GBq/μmol. Quantitative autoradiography with [18F]AM-10 in sagittal mouse brain cryostat sections indicated a maximum specific binding (Bmax) of 15.8 ± 2.8 pmol/g of wet weight and a dissociation constant (KD) of 16.6 ± 5.1 nM. Thus, we present the first synthesis of [18F]AM-10 by isotopic exchange and confirm its specific binding at mouse brain P2X7 receptors, which should warrant its use in animal and human PET investigations.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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