Impact of Reference and Target Region Selection on Amyloid PET SUV Ratios in the Phase 1b PRIME Study of Aducanumab
| Autor: | Barry J. Bedell, John O'Gorman, Tianle Chen, Marilyn Grand'Maison, Paul O’Neill, Alex P. Zijdenbos, Brian B. Avants, Ping Chiao, Robert A. Koeppe |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Amyloid Cerebellum Antibodies Monoclonal Humanized White matter 03 medical and health sciences 0302 clinical medicine Cortex (anatomy) Image Processing Computer-Assisted medicine Humans Radiology Nuclear Medicine and imaging Anterior cingulate cortex business.industry Biological Transport Reference Standards medicine.disease Pons 030104 developmental biology medicine.anatomical_structure Positron-Emission Tomography Brain size Female Aducanumab Alzheimer's disease business Nuclear medicine 030217 neurology & neurosurgery |
| Zdroj: | Journal of Nuclear Medicine. 60:100-106 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.118.209130 |
| Popis: | SUV ratios (SUVRs) are commonly used to quantify tracer uptake in amyloid-β PET. Here, we explore the impact of target and reference region-of-interest (ROI) selection on SUVR effect sizes using interventional data from the ongoing phase 1b PRIME study (NCT01677572) of aducanumab (BIIB037) in patients with prodromal or mild Alzheimer disease. Methods: The florbetapir PET SUVR was calculated at baseline (screening) and at weeks 26 and 54 for patients randomized to receive placebo and each of 4 aducanumab doses (1, 3, 6, and 10 mg/kg) using the whole cerebellum, cerebellar gray matter, cerebellar white matter, pons, and subcortical white matter as reference regions. In addition to the prespecified composite cortex target ROI, individual cerebral cortical ROIs were assessed as targets. Results: Of the reference regions used, subcortical white matter, cerebellar white matter, and the pons, alone or in combination, generated the largest effect sizes. The use of the anterior cingulate cortex as a target ROI resulted in larger effect sizes than the use of the composite cortex. SUVR calculations were not affected by correction for brain volume changes over time. Conclusion: Dose- and time-dependent reductions in the amyloid PET SUVR were consistently observed with aducanumab only in cortical regions prone to amyloid plaque deposition, regardless of the 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 the amyloid burden in patients with Alzheimer disease. |
| Databáze: | OpenAIRE |
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