title: Prediction of the Clinical SUV Ratio in Amyloid PET Imaging Using a Biomathematic Modeling Approach Toward the Efficient Development of a Radioligand.
abstract: Our study aimed to develop a method to mathematically predict the kinetic parametersK1(influx rate constant),k2(efflux rate constant), and BPND(nondisplaceable binding potential) of amyloid PET tracers and obtain SUV ratios (SUVRs) from predicted time-activity curves of target and reference regions.Methods:We investigated 10 clinically applied amyloid PET radioligands:11C-Pittsburgh compound B,11C-BF-227,11C-AZD2184,11C-SB-13,18F-FACT,18F-florbetapir,18F-florbetaben,18F-flutemetamol,18F-FDDNP, and18F-AZD4694. For each tracer, time-activity curves of both target and reference regions were generated using a simplified 1-tissue-compartment model, with an arterial plasma input function and the predicted kinetic parameters.K1,k2, and BPNDwere derived from the lipophilicity (logP), apparent volume, free fraction in plasma, free fraction in tissue, dissociation constant, and density of amyloid β using biomathematic modeling. Density was fixed at 3 nM to represent healthy control conditions and 50 nM to represent severe Alzheimer disease (AD). Predicted SUVRs for the healthy and AD groups were then obtained by dividing the integrated time-activity curve of the target region by that of the reference region. To validate the presented method, the predictedK1,k2, BPND, and SUVR for the healthy and AD groups were compared with the respective clinically observed values.Results:The correlation between predicted and clinical kinetic parameters had anR2value of 0.73 forK1in the healthy group, 0.71 forK1in the AD group, 0.81 fork2in the healthy group, 0.85 fork2in the AD group, and 0.63 for BPNDin the AD group. The regression relationship between the predicted SUVR (y) and the clinical SUVR (x) for the healthy and the AD groups wasy= 2.73x- 2.11 (R2= 0.72).Conclusion:The proposed method showed a good correlation between predicted and clinical SUVR for the 10 clinically applied amyloid tracers.
authors.affiliation: Department of Medical Physics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Arakawa
authors.affiliation: Division of Radiation Protection and Safety Control, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: YingHwey
authors.initials: Y
authors.lastname: Nai
authors.affiliation: Department of Medical Physics, Tohoku University Graduate School of Medicine, Sendai, Japan shidahara@med.tohoku.ac.jp.|Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Shidahara
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.affiliation: Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Seki
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan; and.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Division of Radiation Protection and Safety Control, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Division of Neuro-Imaging, Institute of Development, Ageing and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan; and.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.affiliation: Department of Medical Physics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Gonda
authors.affiliation: Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D001692:Biological Transport; D055808:Drug Discovery; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008954:Models, Biological; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000682:Amyloid; D008024:Ligands; D019275:Radiopharmaceuticals
keywords: amyloid imaging; biomathematical modeling; positron emission tomography; standardized uptake value ratio