PROGRESS IN DEVELOPING A LIGHT-STABLE 4R TAU PET IMAGING AGENT: APN-1701 FIH

Background: The need for a light stable 4R tau PET tracer for use in diverse tauopathies is widely appreciated. We aimed to assess the initial human imaging profile of [18F]APN-1701 as such a tracer and to compare its imaging profile to the well-established but light-sensitive tracer [18F]-APN-1607 that can detect 4R aggregates as well as 3R and mixed 3R/4R aggregates. [18F]APN-1607 has progressed to a multicenter Phase 2 clinical trial for Alzheimer’s disease (AD); therefore, prior imaging data with it was considered valuable for comparison. Method: One cognitively normal (CN) subject (male, 73yo) and one AD subject (female, 58 yo), who had undergone prior amyloid profiling using [18F]florbetapir PET and subsequent imaging with [18F]APN-1607 in a proof-of-concept study and a test-retest study, respectively, participated in the current study. Dynamic imaging with [18F]APN-1701 was performed over 180 min to obtain kinetic data. Result: Overall, for both subjects [18F]APN-1701 generally matched [18F]APN-1607 findings, i.e., peak SUV values reached similar levels. The CN subject, who was amyloid negative, had slight, uniform cortical [18F]-APN-1701 uptake and more substantial uptake in the pallidum, pons and midbrain. SUVr images for the AD subject showed retention in similar brain regions for both tau tracers with the same rank order of regional SUV/SUVr. Notably, for this subject [18F]APN-1701 continued to accumulate up to the end of image acquisition. Conclusion: [18F]APN-1701 demonstrates cortical uptake generally similar to [18F]APN-1607 but its slow kinetics are unfavorable for further development.