Early-Phase ¹⁸F-Florbetapir and ¹⁸F-Flutemetamol Images as Proxies of Brain Metabolism in a Memory Clinic Setting

Abstract

Alzheimer disease (AD) neuropathologic changes are β-amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual-phase amyloid PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early-phase amyloid PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, whereas the late frames depict amyloid distribution. Our study aimed to assess the comparability between early-phase amyloid PET scans and ¹⁸F-FDG PET brain topography at the individual level and their ability to discriminate patients. Methods: One hundred sixty-six subjects evaluated at the Geneva Memory Center, ranging from no cognitive impairment to mild cognitive impairment and dementia, underwent early-phase amyloid PET—using either ¹⁸F-florbetapir (eFBP) (n = 94) or ¹⁸F-flutemetamol (eFMM) (n = 72)—and ¹⁸F-FDG PET. Aβ status was assessed. SUV ratios (SUVRs) were extracted to evaluate the correlation of eFBP/eFMM and their respective ¹⁸F-FDG PET scans. The single-subject procedure was applied to investigate hypometabolism and hypoperfusion maps and their spatial overlap by the Dice coefficient. Receiver-operating-characteristic analyses were performed to compare the discriminative power of eFBP/eFMM and ¹⁸F-FDG PET SUVR in AD-related meta–regions of interest between Aβ-negative healthy controls and cases in the AD continuum. Results: Positive correlations were found between eFBP/eFMM and ¹⁸F-FDG PET SUVR independently of Aβ status and Aβ radiotracer (R > 0.72, P < 0.001). eFBP/eFMM single-subject analysis revealed clusters of significant hypoperfusion with good correspondence to hypometabolism topographies, independently of the underlying neurodegenerative patterns. Both eFBP/eFMM and ¹⁸F-FDG PET SUVR significantly discriminated AD patients from controls in the AD-related meta–regions of interest (eFBP area under the curve [AUC], 0.888; eFMM AUC, 0.801), with ¹⁸F-FDG PET performing slightly better, although not significantly (all P values higher than 0.05), than others (¹⁸F-FDG AUC, 0.915 and 0.832 for subjects evaluated with eFBP and eFMM, respectively). Conclusion: The distribution of perfusion was comparable to that of metabolism at the single-subject level by parametric analysis, particularly in the presence of a high neurodegeneration burden. Our findings indicate that eFBP and eFMM imaging can replace ¹⁸F-FDG PET imaging, as they reveal typical neurodegenerative patterns or allow exclusion of the presence of neurodegeneration. The findings show cost-saving capacities of amyloid PET and support routine use of the modality for individual classification in clinical practice.