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Comparison of Early-Phase 11C-Deuterium-L-Deprenyl and 11C-PiB PET for Assessing Brain Perfusion in Alzheimer's Disease.

Rodriguez-Vieitez, Elena; Carter, Stephen F; Chiotis, Konstantinos; Saint-Aubert, Laure; Leuzy, Antoine; Schöll, Michael; Almkvist, Ove; Wall, Anders; Langström, Bengt; Nordberg, Agneta

The PET tracer 11C-deuterium-L-deprenyl (11C-DED) has been used to visualize activated astrocytes in vivo in patients with Alzheimer's disease (AD). In this multitracer PET study, early-phase 11C-DED and 11C-Pittsburgh compound-B (11C-PiB) (eDED and ePiB, respectively) were compared as surrogate markers of brain perfusion, and the extent to which 11C-DED binding is influenced by brain perfusion was investigated.

METHODS: 11C-DED, 11C-PiB and 18F-fluorodeoxyglucose (FDG) dynamic PET scans were performed in age-matched groups comprising AD patients (n = 8), patients with mild cognitive impairment (MCI, n = 17), and healthy controls (HC, n = 16). A modified-reference Patlak model was used to quantify 11C-DED binding. A Simplified Reference Tissue Model was applied to both 11C-DED and 11C-PiB to measure brain perfusion relative to the cerebellar gray matter (GM) (R1) and binding potentials. 11C-PiB retention and 18F-FDG uptake were also quantified as target-to-pons standardized uptake value ratios in 12 regions of interest (ROIs).

RESULTS: The strongest within-subject correlations with the corresponding R1 values (R1,DED and R1,PiB, respectively) and with 18F-FDG uptake were obtained when the eDED and ePiB PET data were measured 1-4 min post-injection. The optimum eDED/ePiB intervals also showed strong, significant ROI-based inter-subject Pearson's correlations with R1,DED/R1,PiB and with 18F-FDG uptake, while 11C-DED binding was largely independent of brain perfusion, as measured by eDED. Corresponding voxelwise correlations confirmed the ROI-based results. Temporo-parietal eDED or ePiB brain perfusion measurements were highly discriminative between patient and control groups, with discriminative ability statistically comparable to that of temporo-parietal 18F-FDG glucose metabolism. Hypometabolism extended over wider regions than hypoperfusion in patient groups compared to controls.

CONCLUSION: The 1-4 min early-frame intervals of 11C-DED or 11C-PiB are suitable surrogate measures for brain perfusion. 11C-DED binding is independent of brain perfusion and thus 11C-DED PET can provide information on both functional (brain perfusion) and pathological (astrocytosis) aspects from a single PET scan. In comparison with glucose metabolism, early-phase 11C-DED and 11C-PiB perfusion appear to provide complementary rather than redundant information.

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