A comparison of multiple amyloid PET radiotracers for Down syndrome clinical trials

TL;DR

This study compares different amyloid PET radiotracers used in Down syndrome clinical trials and finds they estimate similar amyloid onset ages despite varying sensitivity.

Contribution

The study provides a direct comparison of amyloid PET radiotracers in Down syndrome, showing consistent amyloid onset age estimates across tracers.

Findings

Pittsburgh compound B showed greater sensitivity to measure longitudinal amyloid change compared to florbetapir.

NAV4694 and Pittsburgh compound B had similar sensitivity to detect longitudinal amyloid increase.

Estimated age at amyloid onset was consistent across all tested radiotracers.

Abstract

Adults with Down syndrome carry high risk of developing Alzheimer’s disease and efforts to include this population in clinical trials remain limited. A barrier to recruitment for anti-amyloid trials includes the availability of the same amyloid PET radiotracer to multiple treatment centres. The objective of the study is to compare longitudinal rates of change between different amyloid PET radiotracers, particularly Pittsburgh compound B and florbetapir, in Down syndrome and to compare the estimated age at amyloid-positivity derived from these radiotracers. Two hundred thirty-seven adults with Down syndrome from the Trial Ready Cohort-Down syndrome and Alzheimer’s Biomarker Consortium-Down syndrome studies were imaged using T1-weighted MRI and using PET images of Pittsburgh compound B, florbetapir, NAV4694 or flutemetamol to screen for amyloid plaque burden. Currently, Pittsburgh compound B and florbetapir have longitudinal data from these cohorts, while NAV4694 has one individual with longitudinal scans and flutemetamol has no available longitudinal data. Pittsburgh compound B displayed a greater effect size to measure amyloid change compared to florbetapir. NAV4694 and Pittsburgh compound B, which are structurally similar compounds, displayed similar sensitivity to measure longitudinal amyloid increase. The estimated age at amyloid onset showed no significant difference between Pittsburgh compound B, florbetapir, NAV4694 or flutemetamol. The findings suggest that different amyloid PET radiotracers provide consistent estimates of amyloid onset age for adults with Down syndrome. Multicentre studies of Alzheimer’s disease therapeutics can utilize multiple amyloid PET radiotracers to facilitate recruitment; however, these radiotracers have different sensitivity to detect longitudinal change.

Zammit et al. report that participants with Down syndrome imaged with Pittsburgh compound B, florbetapir, NAV4694 or flutemetamol show no difference in age at amyloid onset despite their different sensitivities to detect amyloid change. They conclude that Alzheimer’s disease clinical trials can utilize multiple amyloid imaging agents to facilitate recruitment.

Graphical Abstract

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