[18F]F13640: a selective agonist PET radiopharmaceutical for imaging functional 5-HT1A receptors in humans.
Eur J Nucl Med Mol Imaging
; 50(6): 1651-1664, 2023 05.
Article
en En
| MEDLINE
| ID: mdl-36656363
ABSTRACT
PURPOSE:
F13640 (a.k.a. befiradol, NLX-112) is a highly selective 5-HT1A receptor ligand that was selected as a PET radiopharmaceutical-candidate based on animal studies. Due to its high efficacy agonist properties, [18F]F13640 binds preferentially to functional 5-HT1A receptors, which are coupled to intracellular G-proteins. Here, we characterize brain labeling of 5-HT1A receptors by [18F]F13640 in humans and describe a simplified model for its quantification.METHODS:
PET/CT and PET-MRI scans were conducted in a total of 13 healthy male volunteers (29 ± 9 years old), with arterial input functions (AIF) (n = 9) and test-retest protocol (n = 8). Several kinetic models were compared (one tissue compartment model, two-tissue compartment model, and Logan); two models with reference region were also evaluated simplified reference tissue model (SRTM) and the logan reference model (LREF).RESULTS:
[18F]F13640 showed high uptake values in raphe nuclei and cortical regions. SRTM and LREF models showed a very high correlation with kinetic models using AIF. As concerns test-retest parameters and the prolonged binding kinetics of [18F]F13640, better reproducibility, and reliability were found with the LREF method. Cerebellum white matter and frontal lobe white matter stand out as suitable reference regions.CONCLUSION:
The favorable brain labeling and kinetic profile of [18F]F13640, its high receptor specificity and its high efficacy agonist properties open new perspectives for studying functionally active 5-HT1A receptors, unlike previous radiopharmaceuticals that act as antagonists. [18F]F13640's kinetic properties allow injection outside of the PET scanner with delayed acquisitions, facilitating the design of innovative longitudinal protocols in neurology and psychiatry. TRIAL REGISTRATION Trial Registration EudraCT 2017-002,722-21.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Serotonina
/
Radiofármacos
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Nucl Med Mol Imaging
Asunto de la revista:
MEDICINA NUCLEAR
Año:
2023
Tipo del documento:
Article
País de afiliación:
Francia