A computational positron emission tomography simulation model for imaging beta-amyloid in mice
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Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
Melvin K Simmons1, Ravindra Manjeshwar, Eric D Agdeppa
1Bioinformatics Laboratory, Molecular Medicine and Biotechnology Program, GE Global Research Center, Niskayuna, NY 12309, USA.
Purpose:
We aimed to develop a computational simulation model for beta-amyloid (Abeta) positron emission tomography (PET) imaging.
Procedures:
Model parameters were set to reproduce levels of Abeta within the PDAPP mouse. Pharmacokinetic curves of virtual tracers were computed and a PET detector simulator was configured for a commercially available preclinical PET-imaging system.
Results:
We modeled the effects of Abeta therapy and tracer affinity on the ability to differentiate Abeta levels by PET. Varying affinity had a significant effect on the ability to quantitate Abeta. Further, PET tracers for Abeta monomers were more sensitive to the therapeutic reduction in Abeta levels than total brain amyloid. Following therapy, the decrease in total brain Abeta corresponded to the slow rate of change in total amyloid load as expected.
Conclusions:
We have developed a first proof-of-concept Abeta-PET simulation model that will be a useful tool in the interpretation of preclinical Abeta imaging data and tracer development.