Abstract
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Objectives: To evaluate a new high affinity and selective imaging agent as a biomarker for the serotonin transporter. Methods: A series of both human and non-human primate SPECT studies were performed following bolus injection of 123-I mZIENT to determine the kinetics of brain uptake and washout. A total of seventeen 123-I mZIENT SPECT studies were performed in two nonhuman primates evaluating the regional brain uptake and washout of radioactivity and the effects of displacement with citalopram over different doses. Control displacement studies were performed with reboxetine and methylphenidate. An initial human study was performed following bolus injection of 5 mCi of 123-I mZIENT serial dynamic SPECT acquisitions were obtained up to 4 h post injection. Results: Serial dynamic SPECT images demonstrate excellent penetrance into brain with initial visualization of cortical regions, thalamus, caudate, midbrain, and cerebellum, corresponding to initial brain blood flow. Specific activity in regions of high SERT density, including the thalamus and midbrain > caudate, which peak later and washout slower than cortical regions and cerebellum. Uptake ratios (thalamus: cerebellum) increase over 3 hours with ratios achieving a peak plateau of 6: 1. Intravenous administration of citalopram iv produces a dose dependent displacement of specific activity in thalamus and midbrain (see figure). Reboxetine and methylphenidate produce no displacement. In humans the kinetics of uptake and washout are slower with peak thalamic: cerebellar uptake occuring after 4 h post injection, when target to background ratios are 2:1 and still increasing. Conclusions: 123-I mZIENT is a promising radiotracer for interrogation of SERT in human and non-human primates.
Research Support (if any): NIMH-5R33 MH066622-05
- Society of Nuclear Medicine, Inc.