INITIAL CLINICAL PET STUDIES WITH THE NOVEL TAU AGENT 18-F PI-2620 IN ALZHEIMER'S DISEASE AND CONTROLS

Objectives: Tau accumulation is a key pathologic feature of Alzheimer’s disease (AD) and other dementias. Recently, positron emission tomography tau probes have been developed for in vivo detection of brain tau load, although quantification is challenging due to high off target binding and slow kinetics. PI-2620 is a novel tracer with an IC50 of 1.8 nM for tau in AD brain homogenate competition-assays and binds specifically to tau deposits on AD brain sections (Braak I-VI), Pick’s and PSP pathology.This study assesses18-F-labelled PI-2620 in AD and healthy volunteers.

Methods: In an ongoing clinical imaging study, participants diagnosed with mild Alzheimer’s (AD), non-AD tauopathies, and healthy volunteers (HV) undergo dynamic PET imaging for approximately 180 minutes following 370 MBq bolus injection of 18F-PI-2620. Venous blood is obtained to characterize the kinetics of parent compound.

Results: Initial imaging data in AD subjects shows robust brain uptake and fast wash-out in non-target regions with peak SUV = 4-4.5. There was no increased uptake seen in choroid plexus, striatum, amygdala, or other regions noted in first generation tau agents. In AD, focal asymmetric uptake was evident in temporal and parietal lobes, precuneus, and cingulate. SUVr time curves demonstrate a plateau at 90-100 min post injection with resultant SUVrs of 2.5-2.8.in abnormal regions Blood data confirmed fast kinetics with 20% of parent compound present at 60 min.

Conclusion: Preliminary PET PI-2620 AD studies demonstrate excellent brain penetrance, favorable kinetics, and high target specificity with low nonspecific binding and high signal in regions of expected tau pathology. Research Support: Piramal Imaging