Characterization of 3 PET tracers for Quantification of Mitochondrial and Synaptic function in Healthy Human Brain: 18F-BCPP-EF, 11C-SA-4503, 11C-UCB-J
File(s)JNM_MINDMAPS_revisedManuscript.pdf (2.23 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Mitochondrial complex 1 (MC1) is involved in maintaining brain bioenergetics, the sigma 1 receptor (σ1R) responds to neuronal stress and synaptic vesicle protein 2A (SV2A) reflects synaptic integrity. Expression of each of these proteins is altered in neurodegenerative diseases. Here we characterise the kinetic behaviour of three positron emission tomography (PET) radioligands 18F-BCPP-EF, 11C-SA-4503 and 11CUCB- J, for the measurement of MC1, σ1R and SV2A, respectively, and determine appropriate analysis workflows for their application in future studies of the in vivo molecular pathology of these diseases. Methods: Twelve human subjects underwent dynamic PET scans including associated arterial blood sampling with each radioligand. A range of kinetic models were investigated to identify an optimal kinetic analysis method for each radioligand and a suitable acquisition duration. Results: All three radioligands readily entered the brain and yielded heterogeneous uptake consistent with the known distribution of the targets. The optimal models determined for the regional estimates of volume of distribution (VT) were multilinear analysis 1 (MA1) and the 2-tissue compartment (2TC) model for 18F-BCPP-EF, MA1 for 11C-SA- 4503, and both MA1 and the 1-tissue compartment (1TC) model for 11C-UCB-J. Acquisition times of 70, 80 and 60 minutes for 18F-BCPP-EF, 11C-SA-4503, 11C-UCB-J, respectively, provided good estimates of regional VT values. An effect of age was observed on 18F-BCPP-EF and 11C-UCB-J signal in the caudate. Conclusion: These ligands can be assessed for their potential to stratify patients or monitor the progression of molecular neuropathology in neurodegenerative diseases.
Date Issued
2020-01-01
Date Acceptance
2019-06-04
Citation
Journal of Nuclear Medicine, 2020, 61 (1), pp.96-103
ISSN
1535-5667
Publisher
Society of Nuclear Medicine
Start Page
96
End Page
103
Journal / Book Title
Journal of Nuclear Medicine
Volume
61
Issue
1
Copyright Statement
© 2020 by the Society of Nuclear Medicine and Molecular Imaging. This research was originally published in JNM. Ayla Mansur et al. Characterization of 3 PET Tracers for Quantification of Mitochondrial and Synaptic Function in Healthy Human Brain: 18F-BCPP-EF, 11C-SA-4503, and 11C-UCB-J. J Nucl Med. January 1, 2020 vol. 61 no. 1 96-103 . © SNMMI.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31324712
PII: jnumed.119.228080
Subjects
Kinetic modelling
Neurodegeneration
Neurology
PET
Radiotracer Tissue Kinetics
endoplasmic reticulum
mitochondria
synapses
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-07-19