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

Mitochondrial complex 1 is involved in maintaining brain bioenergetics; σ-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-¹⁸F-BCPP-EF, ¹¹C-SA-4503, and ¹¹C-UCB-J-for the measurement of mitochondrial complex 1, σ-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. <b>Methods:</b> 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. <b>Results:</b> 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 ¹⁸F-BCPP-EF, MA1 for ¹¹C-SA-4503, and both MA1 and the 1-tissue-compartment model for ¹¹C-UCB-J. Acquisition times of 70, 80, and 60 min for ¹⁸F-BCPP-EF, ¹¹C-SA-4503, ¹¹C-UCB-J, respectively, provided good estimates of regional volume of distribution values. An effect of age was observed on ¹⁸F-BCPP-EF and ¹¹C-UCB-J signal in the caudate. <b>Conclusion:</b> These ligands can be assessed for their potential to stratify patients or monitor the progression of molecular neuropathology in neurodegenerative diseases.