Name
Title | ||
|---|---|---|
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. |
Abstract | ||
|---|---|---|
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.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.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.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. |
Year | DOI | Venue |
|---|---|---|
2012 | 10.1016/j.neuroimage.2011.07.001 | NeuroImage |
Keywords | Field | DocType |
11C-MDL100907,5-HT2A receptors,Positron emission tomography (PET),Test–retest,Endogenous competition,Rapid tryptophan depletion | Nuclear medicine,Serotonin,Receptor antagonist,Developmental psychology,Internal medicine,Psychology,5-HT receptor,Receptor,Human brain,Orbitofrontal cortex,Endocrinology,Binding potential,Temporal lobe | Journal |
Volume | Issue | ISSN |
59 | 1 | 1053-8119 |
Citations | PageRank | References |
2 | 0.46 | 0 |
Authors | ||
7 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Peter S. Talbot | 1 | 4 | 1.18 |
| Mark Slifstein | 2 | 2 | 3.84 |
| Dah-Ren Hwang | 3 | 2 | 0.80 |
| Yiyun Huang | 4 | 2 | 3.84 |
| Erica Scher | 5 | 2 | 0.46 |
| Anissa Abi-Dargham | 6 | 2 | 3.17 |
| Marc Laruelle | 7 | 24 | 7.53 |