Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [ <superscript>11</superscript> C]AFM. - OpacWWW

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Tytuł:: Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [ C]AFM.
Autorzy:: Fang H; PET Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA. .; Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. .
Rossano S; PET Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Wang X; Cellular Neuroscience, Neurodegeneration, and Repair Program, and Departments of Neurology and Neurobiology, Yale School of Medicine, New Haven, CT, USA.
Nabulsi N; PET Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Kelley B; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
Fowles K; PET Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Ropchan J; PET Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Strittmatter SM; Cellular Neuroscience, Neurodegeneration, and Repair Program, and Departments of Neurology and Neurobiology, Yale School of Medicine, New Haven, CT, USA.
Carson RE; PET Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
Huang Y; PET Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA. .
Źródło:: Molecular imaging and biology [Mol Imaging Biol] 2022 Aug; Vol. 24 (4), pp. 560-569. Date of Electronic Publication: 2022 Jan 12.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 2005- : New York, NY : Springer
Original Publication: New York, NY : Elsevier Science, c2001-
MeSH Terms:: Serotonin Plasma Membrane Transport Proteins*/metabolism
Spinal Cord Injuries*/diagnostic imaging
Spinal Cord Injuries*/metabolism
Animals ; Citalopram ; Humans ; Indicators and Reagents ; Positron-Emission Tomography/methods ; Rats ; Serotonin/metabolism ; Spinal Cord/diagnostic imaging ; Tissue Distribution
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Grant Information:: R35 NS097283 United States NS NINDS NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS
Contributed Indexing:: Keywords: PET imaging; Serotonin transporter; Spinal cord injury; [11C]AFM
Substance Nomenclature:: 0 (Indicators and Reagents)
0 (Serotonin Plasma Membrane Transport Proteins)
0DHU5B8D6V (Citalopram)
333DO1RDJY (Serotonin)
Entry Date(s):: Date Created: 20220112 Date Completed: 20220721 Latest Revision: 20230802
Update Code:: 20240104
PubMed Central ID:: PMC9550197
DOI:: 10.1007/s11307-021-01698-7
PMID:: 35020138
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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 [ 11 C]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 [ 11 C]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 [ 11 C]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 [ 11 C]AFM in healthy rats. About 65% of [ 11 C]AFM uptake in the spinal cord was blocked by citalopram. In the SCI rat model, the cervical uptake of [ 11 C]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, [ 11 C]AFM uptake in the human spinal cord showed no obvious decrease after treatment with citalopram. In the human subjects with SCI, decreases in [ 11 C]AFM uptake were also not obvious in the section of spinal cord caudal to the injury point.
Conclusion: [ 11 C]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 [ 11 C]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.
(© 2022. World Molecular Imaging Society.)

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