Journal
BIOLOGICAL PSYCHIATRY
Volume 59, Issue 9, Pages 821-828Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2005.08.010
Keywords
PET; SSRI; reference region; cerebellum
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Background: In vivo determination of serotonin transporter (5-HTT) occupancy by selective serotonin reuptake inhibitors (SSRI) using positron emission tomography (PET) can aid in determination of closing. Previous studies used chronic SSRI administration that may down-regulate 5-HTT and used the cerebellum as reference region despite measurable 5-HTT. We examine the reference region and occupancy after acute sertraline dosing. Methods: We conducted autoradiography of human postmortem cerebellum. to determine an optimal reference region. We quantified 5-HTT binding using [C-11]DASB and arterial input functions in 17 healthy volunteers. Baseline PET scans were followed by a scan 4-6 days after 25 mg to 100mg of daily sertraline. Several modeling methods and outcome measures were assessed. Results: Cerebellar gray matter is the optimal reference region. Occupation of 5-HTT sites saturates at low plasma sertraline levels (K-D =.1.9 ng/ml) with maximal occupancies of 106.8 +/- 8.3% across all brain regions. There is a weak correlation between oral sertraline and plasma sertraline. Occupancy measures vary based on the reference region and outcome measure used. Conclusions: Occupancy studies and postmortem autoradiography can help define the optimal reference region. Reference tissue modeling using the optimal reference region returns the same occupancy measures as those determined using an arterial input function.
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