Format

Send to

Choose Destination
J Nucl Med. 2018 May 18. pii: jnumed.118.209130. doi: 10.2967/jnumed.118.209130. [Epub ahead of print]

Impact of Reference/Target Region Selection on Amyloid PET Standard Uptake Value Ratios in the Phase 1b PRIME Study of Aducanumab.

Author information

1
Biogen, United States.
2
Biospective Inc., Canada.
3
Biospective Inc, Canada.
4
Complete Medical Communications, United Kingdom.
5
University of Michigan, United States.

Abstract

Standardized uptake value ratios (SUVRs) are commonly used to quantify tracer uptake in amyloid beta positron emission tomography (Aβ-PET). Here, we explore the impact of target and reference region of interest (ROI) selection on SUVR effect size using interventional data from the ongoing Phase Ib PRIME study (NCT01677572) of aducanumab (BIIB037) in patients with prodromal or mild Alzheimer's disease (AD). Methods: Florbetapir PET SUVR was calculated at baseline (screening) and Weeks 26 and 54 for patients randomized to placebo and each of four aducanumab doses (1, 3, 6, and 10 mg/kg), using whole cerebellum, cerebellar grey matter, cerebellar white matter, pons, and subcortical white matter as reference regions. In addition to the pre-specified composite cortex target ROI, individual cerebral cortical ROIs were assessed as targets. Results: Of the reference regions used, subcortical white matter, cerebellum white matter, or pons, alone or in combination, generated the largest effect sizes. The use of anterior cingulate cortex as target ROI resulted in greater effect sizes than composite cortex. SUVR calculations were not affected by correction for brain volume change over time. Conclusion: Dose- and time-dependent reductions in amyloid PET SUVR were consistently observed with aducanumab only in cortical regions prone to amyloid plaque deposition, regardless of amyloid-plaque-devoid reference region used. These data support the hypothesis that florbetapir SUVR responses associated with aducanumab treatment are a result of specific dose- and time-dependent reductions in amyloid burden in patients with AD.

KEYWORDS:

Alzheimer’s disease; Neurology; PET/MRI; Research Methods; SUVR; aducanumab; amyloid PET; amyloid beta

PMID:
29777003
DOI:
10.2967/jnumed.118.209130

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center