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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/61989592:15110/25:73631714 RIV/60461373:22330/25:43932318 RIV/60461373:22340/25:43932318 RIV/00098892:_____/25:10159400

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Omega

ISSN

2470-1343

e-ISSN

2470-1343

Svazek periodika

10

Číslo periodika v rámci svazku

32

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

36340-36350

Kód UT WoS článku

001545193700001

EID výsledku v databázi Scopus

2-s2.0-105024417498