Characterization of 3 PET Tracers for Quantification of Mitochondrial and Synaptic Function in Healthy Human Brain: F-18-BCPP-EF, C-11-SA-4503, and C-11-UCB-J

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  • MIND-MAPS Consortium

Mitochondrial complex 1 is involved in maintaining brain bioenergetics; sigma-1 receptor responds to neuronal stress; and synaptic vesicle protein 2A reflects synaptic integrity. Expression of each of these proteins is altered in neurodegenerative diseases. Here, we characterize the kinetic behavior of 3 PET radioligands-F-1(8)-BCPP-EF, C-11-SA-4503, and C-11-UCB-J-for the measurement of mitochondrial complex 1, sigma-1 receptor, and synaptic vesicle protein 2A, 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 with each radioligand, including associated arterial blood sampling. A range of kinetic models was investigated to identify an optimal kinetic analysis method for each radioligand and a suitable acquisition duration. Results: All 3 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 were multilinear analysis 1 (MA1) and the 2-tissue-compartment model for F-18-BCPP-EF, MA1 for C-11-SA-4503, and both MA1 and the 1-tissue-compartment model for C-11-UCB-J. Acquisition times of 70, 80, and 60 min for F-18-BCPP-EF, C-11-SA-4503, C-11-UCB-J, respectively, provided good estimates of regional volume of distribution values. An effect of age was observed on F-18-BCPP-EF and C-11-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.

OriginalsprogEngelsk
TidsskriftJournal of Nuclear Medicine
Vol/bind61
Nummer1
Sider (fra-til)96-103
Antal sider8
ISSN0161-5505
DOI
StatusUdgivet - 1 jan. 2020
Eksternt udgivetJa

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