PET Quantification of ¹⁸F-Florbetaben Binding to β-Amyloid Deposits in Human Brains

Abstract

18 F-florbetaben is a novel 18 F-labeled tracer for PET imaging of b-amyloid deposits in the human brain. We evaluated the kinetic model-based approaches to the quantification of b-amyloid binding in the brain from dynamic PET data. The validity of the practically useful tissue ratio was also evaluated against the model-based parameters. Methods: 18 F-florbetaben PET imaging was performed with concurrent multiple arterial sampling after tracer injection (300 MBq) in 10 Alzheimer disease (AD) patients and 10 age-matched healthy controls. Regional brain-tissue time-activity curves for 90 min were analyzed by a 1-tissue-compartment model and a 2-tissue-compartment model (2TCM) with metabolite-corrected plasma data estimating the specific distribution volume (V S ) and distribution volume ratio (DVR [2TCM]) and a multilinear reference tissue model estimating DVR (DVR [MRTM]) using the cerebellar cortex as the reference tissue. Target-to-reference tissue standardized uptake value ratios (SUVRs) at 70-90 min were also calculated. Results: All brain regions required 2TCM to describe the timeactivity curves. All b-amyloid binding parameters in the cerebral cortex (V S , DVR [2TCM], DVR [MRTM], and SUVR) were significantly increased in AD patients (P , 0.05), and there were significant linear correlations among these parameters (r 2 . 0.83). Effect sizes in group discrimination between 8 b-amyloidpositive AD scans and 9 b-amyloid-negative healthy control scans for all binding parameters were excellent, being largest for DVR (2TCM) (4.22) and smallest for V S (3.25) and intermediate and the same for DVR (MRTM) and SUVR (4.03). Conclusion: These results suggest that compartment kinetic model-based quantification of b-amyloid binding from 18 Fflorbetaben PET data is feasible and that all b-amyloid binding parameters including SUVR are excellent in discriminating between b-amyloid-positive and -negative scans.

Improved Power for Characterizing Longitudinal Amyloid-β PET Changes and Evaluating Amyloid-Modifying Treatments with a Cerebral White Matter Reference Region

“…PET ligands (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) have made it possible to investigate the fibrillar amyloid-b (Ab) burden in living people; to clarify its relationship to the dementia, mild cognitive impairment (MCI), and preclinical stages of Alzheimer disease (AD); to characterize the extent to which cross-sectional measurements predict subsequent clinical declines; to track longitudinal changes; and to help evaluate Ab-modifying treatments.…”

Standardized Expression of 18F-NAV4694 and 11C-PiB β-Amyloid PET Results with the Centiloid Scale

“…Results vary for each of the available tracers because of differences in their specific and nonspecific binding properties and in their recommended reference regions (2)(3)(4)(5). Results are also influenced by the timing of the acquisition after tracer administration, the duration of the acquisition, the image reconstruction algorithm used, whether partial-volume correction is applied, the choice and extent of cortical regions, and the type of quantitative method used, such as SUV ratio (SUVR), distribution volume ratio, or binding potential (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Consequently, most imaging labs have had to derive a reference range for their method and tracers or rely on subjective visual interpretation.…”

The role of PET quantification in neurological imaging: FDG and amyloid imaging in dementia

“…Static uptake ratios (SUVRs) compared well with respect to test-retest, but are subject to a systematic bias that depends on measurement time. Correlations between cortical SUVRs (static scans) and DVRs (dynamic scans) for amyloid tracers are generally high in cross-sectional studies [56,58,59], and assessment of SUVRs has therefore generally been accepted as a practical standard for the use of PET as diagnostic biomarker that does not require dynamic scanning [60]. However, this notion has recently been challenged, especially when using amyloid PET for monitoring of disease progression, because SUVRs are likely to be biased by changes in regional blood flow [61].…”