Dual-biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and¹¹C-Labeled Pittsburgh compound B

PET studies with biomarkers of regional neuronal activity (cerebral glucose metabolism or blood flow [CBF]) and amyloid-β (Aβ) depositions provide complementary information for the early diagnosis of dementia and follow-up of patients with dementia. We investigated the validity of relative regional CBF estimates (R₁) gained from pharmacokinetic analyses of ¹¹C-labeled Pittsburgh compound B (¹¹C-PIB) PET studies as a marker of neuronal activity and neurodegeneration. Methods: Twenty-two patients with cognitive impairment (16 patients with early Alzheimer disease) underwent ¹⁸F-FDG and ¹¹C-PIB PET studies for the assessment of regional glucose metabolism and Aβ load. Parametric images of R₁ (relative CBF) and binding potential (BP_ND; Aβ load) were generated by 2-step simplified reference tissue model (SRTM2) analyses of dynamic ¹¹C-PIB data. Volume-of-interest and voxel-based statistical analyses were performed to investigate the association between normalized ¹⁸F-FDG uptake and ¹¹C-PIB R₁ and the correlation of these measures with symptom severity (Mini-Mental State Examination [MMSE] scores) in patients with Alzheimer disease. Results: SRTM2 analyses provided high-quality ¹¹C-PIB R₁ images that were comparable to ¹⁸F-FDG PET images. Regional ¹¹C-PIB R ₁ values strongly correlated with normalized regional ¹⁸F-FDG uptake when correlations were calculated separately for each patient (R² [mean ± SD], 0.73 ± 0.11) or across all regions of all patients (R², 0.62). A regression model including ¹⁸F-FDG uptake, subject identification, and region grouping (into cortical, subcortical, and limbic regions to allow for possible differences in flow/metabolism coupling) accounted for 86% of total ¹¹C-PIB R ₁ variability. Voxel-based correlation analyses of ¹⁸F-FDG uptake and ¹¹C-PIB R₁ with MMSE scores revealed similar core findings of positive correlations in the posterior cingulate gyrus/precuneus and negative correlations (preserved activity) in the bilateral sensorimotor cortex. There was no correlation between Aβ load (BP _ND) and MMSE scores. Conclusion: These results strongly suggest that ¹¹C-PIB R₁ can serve as a complementary biomarker of neuronal activity and, thus, neurodegeneration in addition to Aβ load given by ¹¹C-PIB BP_ND. Further studies are needed to validate the diagnostic value of dual-biomarker ¹¹C-PIB PET studies in comparison with combined ¹⁸F-FDG and ¹¹C-PIB PET studies. Compared with the latter, dual-biomarker ¹¹C-PIB PET greatly reduces costs and burden for patients.