EVALUATION OF [F-18]-PI-2620, A SECOND-GENERATION SELECTIVE TAU TRACER, FOR THE ASSESSMENT OF ALZHEIMER’S AND NON-ALZHEIMER’S TAUOPATHIES

Abstract

Most first-generation tau tracers bind to the typical 3R/4R tau deposits prevalent in Alzheimer's disease (AD). These first-generation tau tracers have varying degrees of “off-target” binding or lack of selectivity for tau. The new tau tracer, 18F-PI-2620 appears unique in that it binds to all types (3R, 4R and 3R/4R) of tau deposits in vitro. The purpose of the study was to assess the ability of 18F-PI-2620 to detect and measure global and regional tau burden in the brain in healthy older controls, AD and non-AD tauopathies such as Progressive Supranuclear Palsy (PSP) and Frontotemporal Lobar Degeneration (FTLD). Participants with clinical diagnosis of probable AD, PSP, FTLD as well as healthy age-matched controls (HC) and participants classified as suffering mild cognitive impairment (MCI), underwent a 50-70 min static scan with 18F-NAV4694 to establish Aβ-status (Aβ-/Aβ+), and 0-120 min dynamic tau imaging with 18F-PI-2620. Global and regional 18F-PI-2620 binding was assessed using Distribution Volume Ratios (DVR), and with standardized uptake value ratios (SUVR), calculated using the cerebellar cortex as reference region. No tracer retention was observed in Aβ-HC. No “off-target” binding in choroid plexus or basal ganglia was observed in any of the participants scanned. In Aβ+AD patients 18F-PI-2620 binding was significantly higher than in HC, with the highest tracer retention in temporoparietal and posterior cingulate areas (Figure 1A). Tracer presented reversible kinetics and apparent steady state was reached ∼80-90 min after 18F-PI-2620 injection (Figure 1B). There was high agreement between regional DVRCbCtx and SUVRCbCtx. Identical classification into tau-/tau+ resulted from semiquantitative measures and visual inspection of the images