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Spect imaging of the serotonin transporter using a novel ligand - 123-I mZIENT - in human subjects - a dosimetry and biodisortribution study

Published online by Cambridge University Press:  16 April 2020

R. Krishnadas ,
A. Nicol ,
S. Champion ,
S. Pimlott ,
J. Stehouwer ,
G. Tamagnan ,
M. Goodman  and
D. Hadley
R. Krishnadas
Affiliation:
Sackler Institute of Psychobiological Research, University of Glasgow, UK
A. Nicol
Affiliation:
Department of Clinical Physics, Greater Glasgow and Clyde NHS Trust UK, UK
S. Champion
Affiliation:
Department of Clinical Neurosciences, University of Glasgow, UK
S. Pimlott
Affiliation:
Radiopharmaceutical Research & Development, NHS Greater Glasgow and Clyde, Glasgow, UK
J. Stehouwer
Affiliation:
Department of Radiology, Emory University, Atlanta, GA
G. Tamagnan
Affiliation:
Institute for Neurodegenerative Disorders, New Haven, CT, USA
M. Goodman
Affiliation:
Department of Radiology, Emory University, Atlanta, GA
D. Hadley
Affiliation:
Department of Neuroradiology, Institute of Neurological Sciences, NHS Greater Glasgow and Clyde, Glasgow, UK

Abstract

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Levels of serotonin in the body are regulated by the serotonin transporters (SERT), which are predominantly located on the presynaptic terminals of serotonin-containing neurons. Alterations in the density of SERT have been implicated in the pathophysiology of many neuropsychiatric disorders.

Aim

To evaluate 123-I mZIENT (2(S)-[(S)-2b-carbomethoxy-3b-[3′-((Z)-2-iodoethenyl)phenyl]nortropane), a novel radiopharmaceutical for imaging SERT. The bio-distribution of the radiopharmaceutical in humans was investigated and dosimetry performed.

Methods

The study includes three healthy volunteers and three patients receiving SSRIs. Whole body images obtained on a gamma camera at 10 minutes, 1, 2, 3, 6, 24 and 48 hours post administration. Dosimetry was performed. ROIs were drawn over the brain, heart, kidneys, liver, lungs, salivary glands, spleen, thyroid and intestines. Blood was sampled at 5, 15, & 30 minutes and 1, 2, 3, 6, 24 and 48 hours post administration. Urine was collected at 1, 2, 3, 4, 6, 24 and 48 hours. Brain SPECT images were obtained using a neuroSPECT scanner at 4 hours, evaluated visually and analysed using ROI analysis.

Results

High quality SPECT images can be obtained after 100–150 MBq 123-ImZEINT. Regional brain uptake was observed in midbrain and basal ganglia in healthy volunteers, consistent with the known distribution of SERT. Biodistribution images demonstrated highest uptake in the lungs, brain, liver and intestines. The effective dose was within range of other commonly used ligands and is acceptable for clinical imaging.

Conclusion

123-ImZIENT is a promising agent for imaging SERT in humans with acceptable dosimetry.

Type
P02-339
Information
European Psychiatry , Volume 26 , Issue S2: Abstracts of the 19th European Congress of Psychiatry , March 2011 , pp. 935
Copyright
Copyright © European Psychiatric Association 2011
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