In Vivo Head-to-Head Comparison of [¹⁸F]GTP1 with [¹⁸F]MK-6240 and [¹⁸F]PI-2620 in Alzheimer Disease

Alzheimer disease (AD) is characterized by the accumulation of tau neurofibrillary tangles that can be labeled with PET tracers. Multiple tau PET tracers have been used in clinical studies, including [¹⁸F]GTP1, [¹⁸F]PI-2620, and [¹⁸F]MK-6240. Standardized harmonization scales for comparing tau PET signals across tracers are currently under development and can be informed by comparisons of signals between tracers in both target and off-target regions of the brain. Methods: We conducted a head-to-head study comparing [¹⁸F]GTP1 with [¹⁸F]PI-2620 and [¹⁸F]MK-6240 in terms of dynamic range, magnitude of uptake, and correlation between tracers in participants with normal cognition and prodromal to mild AD. Results: [¹⁸F]GTP1 exhibited retention patterns that correlated with [¹⁸F]PI-2620 and [¹⁸F]MK-6240 for all Braak regions (except Braak II). Differences in tracer binding in AD target regions were relatively small, and off-target binding profiles were unique to each tracer. Conclusion: Our findings indicate that [¹⁸F]GTP1, [¹⁸F]PI-2620, and [¹⁸F]MK-6240 display similar uptake patterns in AD patients, suggesting that they detect the same tau pathology. However, the tracer-specific off-target signal distribution may impact their direct comparability, and for some use cases, tracer-specific considerations should be taken into account in the development of a standardized harmonization scale for tau PET.