A computational positron emission tomography simulation model for imaging beta-amyloid in mice

Purpose: We aimed to develop a computational simulation model for beta-amyloid (A beta) positron emission tomography (PET) imaging. Procedures: Model parameters were set to reproduce levels of A beta 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 A therapy and tracer affinity on the ability to differentiate A beta levels by PET. Varying affinity had a significant effect on the ability to quantitate A beta. Further, PET tracers for A beta monomers were more sensitive to the therapeutic reduction in A beta levels than total brain annyloid. Following therapy, the decrease in total brain A beta corresponded to the slow rate of change in total amyloid load as expected. Conclusions: We have developed a first proof-of-concept A beta-PET simulation model that will be a useful tool in the interpretation of preclinical A beta imaging data and tracer development.