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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 4/2022

12-01-2022 | Positron Emission Tomography | Research Article

Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM

Authors: Hanyi Fang, Samantha Rossano, Xingxing Wang, Nabeel Nabulsi, Brian Kelley, Krista Fowles, Jim Ropchan, Stephen M. Strittmatter, Richard E. Carson, Yiyun Huang

Published in: Molecular Imaging and Biology | Issue 4/2022

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Abstract

Purpose

The descending raphespinal serotonin (5-HT) system contributes to neural activities required for locomotion. The presynaptic serotonin transporter (SERT) is a marker of 5-HT innervation. In this study, we explored the use of PET imaging with the SERT radioligand [11C]AFM as a biomarker of 5-HT axon damage after spinal cord injury (SCI) in a rodent model and its translation to imaging SCI in humans.

Procedures

PET imaging with [11C]AFM was performed in healthy rats under baseline and citalopram blocking conditions and a mid-thoracic transection rat model of SCI. The lumbar-to-cervical activity (L/C) ratio was calculated for the healthy and SCI animals to assess SERT binding decrease after SCI. Finally, translation of [11C]AFM PET was attempted to explore its potential to image SCI in humans.

Results

Intense uptake in the brain and intact spinal cord was observed at 30–60 min post-injection of [11C]AFM in healthy rats. About 65% of [11C]AFM uptake in the spinal cord was blocked by citalopram. In the SCI rat model, the cervical uptake of [11C]AFM was similar to that in healthy rats, but the lumbar uptake was dramatically reduced, resulting in about half the L/C ratio in SCI rats compared to healthy rats. In contrast, [11C]AFM uptake in the human spinal cord showed no obvious decrease after treatment with citalopram. In the human subjects with SCI, decreases in [11C]AFM uptake were also not obvious in the section of spinal cord caudal to the injury point.

Conclusion

[11C]AFM PET imaging of SERT provides a useful preclinical method to non-invasively visualize the rodent spinal cord and detect SERT changes in SCI rodent models. However, there appears to be little detectable specific binding signal for [11C]AFM in the human spinal cord. An SERT tracer with higher affinity and lower non-specific binding signal is needed to image the spinal cord in humans and to assess the axonal status in SCI patients.
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Metadata
Title
Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM
Authors
Hanyi Fang
Samantha Rossano
Xingxing Wang
Nabeel Nabulsi
Brian Kelley
Krista Fowles
Jim Ropchan
Stephen M. Strittmatter
Richard E. Carson
Yiyun Huang
Publication date
12-01-2022
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 4/2022
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-021-01698-7

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