Publication date: Mar 19, 2020
Development of medications selective for dopamine D or D receptors is an active area of research in numerous neuropsychiatric disorders including addiction and Parkinson’s disease. The positron emission tomography (PET) radiotracer [C]-(+)-PHNO, an agonist that binds with high affinity to both D and D receptors, has been used to estimate relative receptor subtype occupancy by drugs based on a priori knowledge of regional variation in the expression of D and D receptors. The objective of this work was to use a data-driven independent component analysis (ICA) of receptor blocking scans to separate D-and D-related signal in [C]-(+)-PHNO binding data in order to improve the precision of subtype specific measurements of binding and occupancy. Eight healthy volunteers underwent [C]-(+)-PHNO PET scans at baseline and at two time points following administration of the D-preferring antagonist ABT-728 (150-1000?mg). Parametric binding potential (BP) images were analyzed as four-dimensional image series using ICA to extract two independent sources of variation in [C]-(+)-PHNO BP. Spatial source maps for each component were consistent with respective regional patterns of D-and D-related binding. ICA-derived occupancy estimates from each component were similar to D-and D-specific occupancy estimated from a region-based approach (intraclass correlation coefficients?>?0.95). ICA-derived estimates of D receptor occupancy improved quality of fit to a single site binding model. Furthermore, ICA-derived estimates of the regional fraction of [C]-(+)-PHNO binding related to D receptors was generated for each subject and values showed good agreement with region-based model estimates and prior literature values. In summary, ICA successfully separated D-and D-related components of the [C]-(+)-PHNO binding signal, establishing this approach as a powerful data-driven method to quantify distinct biological features from PET data composed of mixed data sources.
Smart, K., Gallezot, J.D., Nabulsi, N., Labaree, D., Zheng, M.Q., Huang, Y., Carson, R.E., Hillmer, A.T., and Worhunsky, P.D. Separating dopamine D and D receptor sources of -(+)-PHNO binding potential: Independent component analysis of competitive binding. 24446. 2020 Neuroimage.