Hetero-aryl bromide precursor fluorine-18 radiosynthesis and preclinical evaluation of a novel positron emission tomography (PET) tracer [18F]GSK1482160.
Bioorg Med Chem
; 73: 116996, 2022 11 01.
Article
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| MEDLINE
| ID: mdl-36126443
ABSTRACT
The purinergic P2X7 receptor (P2X7R), an ATP gated ion channel, is an important therapeutic target for various inflammatory immune and neurodegenerative diseases. A novel P2X7R targeting radiotracer GSK1482160 was radiosynthesized by hetero-aryl bromides precursor 10 with [18F]Et4NF, 20-30 % radiochemical yield, > 68 GBq/µmol specific activity, >98 % radiochemical purity. Evaluation in healthy male Sprague-Dawley rats revealed that [18F]GSK1482160 ([18F]11) was stably retained 87.81 %, 72.45 %, and 56.32 % in brain, blood and liver respectively 60-min post-injection. Ex-vivo biodistribution of [18F]11 proved that it was able to target the P2X7R in vivo and there was no defluorination in the major organs. PET/MRI imaging and autoradiography revealed that [18F]11 was able to penetrate the blood-brain barrier (BBB) and to be a promising P2X7R PET radioligand for clinical translation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Bromuros
/
Receptores Purinérgicos P2X7
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2022
Tipo del documento:
Article