Comparison of amyloid PET acquired through standardized and unstandardized protocols

Karly A Cody, Andrzej Sokolowski, Lucah Medina Guerra, Philip S Insel, William J Jagust, Theresa M Harrison, Elizabeth C Mormino

Alzheimers Dement. 2025 Sep;21(9):e70697. doi: 10.1002/alz.70697.

ABSTRACT

INTRODUCTION: Amyloid positron emission tomography (PET) scans collected by Alzheimer's Disease Research Centers (ADRCs) include site-specific "mixed protocols" and, since 2021, standardized protocols through the Standardized, Centralized AD/ADRD Neuroimaging initiative. We compared amyloid PET from cohorts using unstandardized versus standardized pre-processing protocols.

METHODS: Across cohorts, amyloid measured in Centiloids (CLs) was derived from 18F-florbetapir (FBP), 18F-florbetaben (FBB), 11C-Pittsburgh compound B (PIB), and 18F-NAV4694 (NAV) scans using identical magnetic resonance imaging-free post-processing pipelines. We evaluated CL distributions across cohorts and tracers using Gaussian mixture models (GMMs).

RESULTS: Within each tracer, GMM-derived amyloid negative (A-) CL distributions were similar across cohorts. PIB and NAV showed lower CL variability in the A- range than FBP and FBB.

DISCUSSION: Consistent post-processing yielded comparable A- distributions within tracer across cohorts with heterogeneous pre-processing protocols, supporting future ADRC PET data integration. Reduced variability in A- classes for PIB and NAV suggest that lower positivity thresholds may be appropriate.

HIGHLIGHTS: Alzheimer's Disease Research Center (ADRC) amyloid positron emission tomography (PET) includes unstandardized and standardized pre-processing. With consistent post-processing, amyloid-negative (A-) Centiloids (CLs) were similar despite variable pre-processing. CLs from 11C-Pittsburgh compound B and 18F-NAV4694 were less variable than 18F-florbetaben and 18F-florbetapir. Similar A- CLs across variable pre-processing supports combining ADRC amyloid PET.

PMID:40983958 | PMC:PMC12453954 | DOI:10.1002/alz.70697