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 dosing. 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 [11C]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 (KD = 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.
Key Words
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Article info
Publication history
Published online: October 07, 2005
Accepted:
August 10,
2005
Received in revised form:
July 27,
2005
Received:
April 12,
2005
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
