PreDiction of the clinical SUV ratio in amyloid PET imaging using a biomathematic modeling approach toward the efficient development of a raDioligand

Yuma Arakawa, Yinghwey Nai, Miho Shidahara, Shozo Furumoto, Chie Seki, Nobuyuki Okamura, Manabu Tashiro, Yukitsuka Kudo, Kazuhiko Yanai, Kohsuke Gonda, Hiroshi Watabe

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Our study aimed to develop a method to mathematically preDict the kinetic parameters K1 (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: 11CPittsburgh compound B, 11C-BF-227, 11C-AZD2184, 11C-SB-13, 18F-FACT, 18F-florbetapir, 18F-florbetaben, 18F-flutemetamol, 18FFDDNP, and 18F-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 BPND were derived from the lipophilicity (logP), apparent volume, free fraction in plasma, free fraction in tissue, Dissociation constant, and density of amyloid b 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 preDicted K1, 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 an R2 value of 0.73 for K1 in the healthy group, 0.71 for K1 in the AD group, 0.81 for k2 in the healthy group, 0.85 for k2 in the AD group, and 0.63 for BPND in the AD group. The regression relationship between the preDicted SUVR (y) and the clinical SUVR (x) for the healthy and the AD groups was y 5 2.73x-2.11 (R2 5 0.72). Conclusion: The proposed method showed a good correlation between preDicted and clinical SUVR for the 10 clinically applied amyloid tracers.

Original languageEnglish
Pages (from-to)1285-1292
Number of pages8
JournalJournal of Nuclear Medicine
Volume58
Issue number8
DOIs
Publication statusPublished - 2017 Aug 1

Keywords

  • Amyloid imaging
  • Biomathematical modeling
  • Positron emission tomography
  • StandarDized uptake value ratio

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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