Extended characterisation of the serotonin 2A (5-HT2A) receptor-selective PET radiotracer 11C-MDL100907 in humans: quantitative analysis, test-retest reproducibility, and vulnerability to endogenous 5-HT tone.
Neuroimage
; 59(1): 271-85, 2012 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-21782029
ABSTRACT
INTRODUCTION:
Scanning properties and analytic methodology of the 5-HT2A receptor-selective positron emission tomography (PET) tracer 11C-MDL100907 have been partially characterised in previous reports. We present an extended characterisation in healthy human subjects.METHODS:
64 11C-MDL100907 PET scans with metabolite-corrected arterial input function were performed in 39 healthy adults (18-55 years). 12 subjects were scanned twice (duration 150 min) to provide data on plasma analysis, model order estimation, and stability and test-retest characteristics of outcome measures. All other scans were 90 min duration. 3 subjects completed scanning at baseline and following 5-HT2A receptor antagonist medication (risperidone or ciproheptadine) to provide definitive data on the suitability of the cerebellum as reference region. 10 subjects were scanned under reduced 5-HT and control conditions using rapid tryptophan depletion to investigate vulnerability to competition with endogenous 5-HT. 13 subjects were scanned as controls in clinical protocols. Pooled data were used to analyse the relationship between tracer injected mass and receptor occupancy, and age-related decline in 5-HT2A receptors.RESULTS:
Optimum analytic method was a 2-tissue compartment model with arterial input function. However, basis function implementation of SRTM may be suitable for measuring between-group differences non-invasively and warrants further investigation. Scan duration of 90 min achieved stable outcome measures in all cortical regions except orbitofrontal which required 120 min. Binding potential (BPP and BPND) test-retest variability was very good (7-11%) in neocortical regions other than orbitofrontal, and moderately good (14-20%) in orbitofrontal cortex and medial temporal lobe. Saturation occupancy of 5-HT2A receptors by risperidone validates the use of the cerebellum as a region devoid of specific binding for the purposes of PET. We advocate a mass limit of 4.6 µg to remain below 5% receptor occupancy. 11C-MDL100907 specific binding is not vulnerable to competition with endogenous 5-HT in humans. Paradoxical decreases in BPND were found in right prefrontal cortex following reduced 5-HT, possibly representing receptor internalisation. Mean age-related decline in brain 5-HT2A receptors was 14.0±5.0% per decade, and higher in prefrontal regions.CONCLUSIONS:
Our data confirm and extend support for 11C-MDL100907 as a PET tracer with very favourable properties for quantifying 5-HT2A receptors in the human brain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Antagonistas da Serotonina
/
Encéfalo
/
Radioisótopos de Carbono
/
Compostos Radiofarmacêuticos
/
Fluorbenzenos
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Humans
/
Middle aged
Idioma:
En
Revista:
Neuroimage
Assunto da revista:
DIAGNOSTICO POR IMAGEM
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos