Kinetic modeling and non-invasive approach for translocator protein quantification with C-DPA-713.

Introduction: C-DPA-713 is a positron emission tomography (PET) radiotracer developed for imaging the expression of the translocator protein (TSPO) in glial cells, which is considered to be a marker of the neuroinflammatory burden. This study investigated the pharmacokinetic profile of C-DPA-713 and evaluated kinetic modeling and non-invasive TSPO quantification using dynamic PET imaging data in the Alzheimer's disease (AD) and cognitive normal (CN) participants.

Methods: Eleven patients with AD and 6 CN participants were examined using dynamic C-DPA-713 PET imaging for 60 min with arterial blood sampling. Time-activity curves were calculated from the cerebellum and three composite regions of interest (ROIs), according to the anatomical definitions of Braak's stages 1 to 3, stage 4, stage 5, and stage 6 that correspond to the pathological stages of tangle deposition. The total distribution volume (V) was evaluated using compartmental modeling and graphical analysis. Reference region-based methods were implemented using an optimal area that was assumed to be void of the radiotracer target as reference tissue.

Results: The concentration of radioactivity in plasma demonstrated rapid clearance. C-DPA-713 peaked rapidly in the gray matter. Compartmental modeling resulted in a good fit, and the one-tissue model with estimated blood volume correction (1Tv) showed the best performance. The estimated V obtained from the graphical plasma methods was highly correlated with that obtained from 1Tv. Reference region-based analysis was conducted using the Braak 6 area as the reference region, and the estimated non-displaceable binding potential was highly correlated with that obtained from 1Tv.

Conclusion: C-DPA-713 possesses properties suitable for TSPO quantification with PET imaging. The Braak 6 area was shown to be a useful reference region in the patients with AD and the CN participants, and non-invasive reference tissue models using the Braak 6 area as a reference region can be employed for TSPO quantification with C-DPA-713-PET imaging as an alternative to the invasive compartmental model.