Quantitative kinetic analysis of PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT in human brain

Nucl Med Biol. 2015 Sep;42(9):734-44. doi: 10.1016/j.nucmedbio.2015.05.001. Epub 2015 May 9.

Abstract

Introduction: The purpose of this study was to compare two amyloid imaging agents, [(11)C]BF227 and [(18)F]FACT (derivative from [(11)C]BF227) through quantitative pharmacokinetics analysis in human brain.

Methods: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients.

Results: For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different.

Conclusion: This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers.

Keywords: Amyloid imaging; Compartment model; [(11)C]BF227; [(18)F]FACT.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Benzoxazoles / pharmacokinetics*
  • Computer Simulation
  • Humans
  • Metabolic Clearance Rate
  • Models, Biological*
  • Molecular Imaging / methods*
  • Neocortex / diagnostic imaging
  • Neocortex / metabolism*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Thiazoles / pharmacokinetics*
  • Tissue Distribution

Substances

  • 2-((2-(2-(2-(dimethylamino)-1,3-thiazol-5-yl)vinyl)-1,3-benzoxazol-6-yl)oxy)-3-fluoropropan-1-ol
  • 2-(2-(2-dimethylaminothiazol-5-yl)ethenyl)-6-(2-(fluoro)ethoxy)benzoxazole
  • Amyloid beta-Peptides
  • Benzoxazoles
  • Radiopharmaceuticals
  • Thiazoles