Appropriate reference region selection of 18F-florbetaben and 18F-flutemetamol beta-amyloid PET expressed in Centiloid

Soo Hyun Cho,Young Ju Kim,Seung Joo Kim,Byeong C Kim,Seung Hwan Moon,Hee Jin Kim,Jun Pyo Kim,Duk L Na,Young Hee Jung,Sang Won Seo,Hyemin Jang,Seongbeom Park,Yeong Sim Choe

doi:10.1038/s41598-020-70978-z

Soo Hyun Cho, Young Ju Kim + Show 11 more

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The Centiloid (CL) is a method for standardizing amyloid beta (Aβ) quantification through different ligands and methods. To find the most appropriate reference region to reduce the variance in the Aβ CL unit between 18F-florbetaben (FBB) and 18F-flutemetamol (FMM), we conducted head-to-head comparisons from 56 participants using the direct comparison of FBB-FMM CL (dcCL) method with four reference regions: cerebellar gray (CG), whole cerebellum (WC), WC with brainstem (WC + B), and pons. The FBB and FMM dcCL units were highly correlated in four reference regions: WC (R2 = 0.97), WC + B (R2 = 0.98), CG (R2 = 0.92), and pons (R2 = 0.98). WC showed the largest effect size in both FBB and FMM. Comparison of the variance of the dcCL values within the young control group showed that with FBB, WC + B had the smallest variance and with FMM, the WC had the smallest variance. Additionally, WC + B showed the smallest absolute difference between FBB and FMM, followed by the WC, pons, and CG. We found that it would be reasonable to use the WC or WC + B as the reference region when converting FBB and FMM SUVRs into dcCL, which can increase the accuracy of standardizing FBB and FMM PET results.

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Amyloid β (Aβ) PET imaging using 11C-Pittsburgh Compound-B (PiB)1, 18F-florbetapir2, 18F-florbetaben (FBB)[3], and 18F-flutemetamol (FMM)[4] has been developed to measure the accumulation of fibrillar beta-Aβ deposition in vivo
To determine which reference region might be appropriate when we combine the FBB and FMM ligands for Aβ imaging, we assessed direct comparison of the FBB-FMM CL (dcCL) units using four different reference regions by making head-to-head comparisons
Our major findings are as follows. Both FBB and FMM had the largest effect size for the dcCL unit when the whole cerebellum (WC) was used as the reference region, followed in order by the cerebellar gray (CG), WC + B, and pons

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Amyloid β (Aβ) PET imaging using 11C-Pittsburgh Compound-B (PiB)1, 18F-florbetapir2, 18F-florbetaben (FBB)[3], and 18F-flutemetamol (FMM)[4] has been developed to measure the accumulation of fibrillar beta-Aβ deposition in vivo. The appropriate reference region can differ with the type of ligand because the 18F-ligands differ in their stability over time[1] and comparable blood flow[6]. The Centiloid (CL) method enables standardized PET-based measurement of the Aβ burden and comparisons of the effect size between AD patients and young controls (YCs) and the variability of Aβ found in the YC group with different types of ligand[10]. We hypothesized that we would find differences in the appropriateness of the different reference regions between FBB and FMM in terms of the largest effect size between the AD and YC groups and the smallest variability within the YC group. We further hypothesized that the absolute dcCL differences between FBB and FMM might vary among the reference regions in single subjects

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