A computational positron emission tomography simulation model for imaging beta-amyloid in mice.
OBJECTIVE
We aimed to develop a computational simulation model for beta-amyloid (Abeta) positron emission tomography (PET) imaging.


METHODS
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.
Simmons
Melvin K
MK
Bioinformatics Laboratory, Molecular Medicine and Biotechnology Program, GE Global Research Center, Niskayuna, NY 12309, USA.
Manjeshwar
Ravindra
R
Agdeppa
Eric D
ED
Mattheyses
Robert M
RM
Kiehl
Thomas R
TR
Montalto
Michael C
MC
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D051379:Mice; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods*; D012680:Sensitivity and Specificity
D016229:Amyloid beta-Peptides