Dual time-point imaging for post-dose binding potential estimation applied to a [11C]raclopride PET dose occupancy study

J Cereb Blood Flow Metab. 2017 Mar;37(3):866-876. doi: 10.1177/0271678X16644463. Epub 2016 Jul 21.

Abstract

Receptor occupancy studies performed with PET often require time-consuming dynamic imaging for baseline and post-dose scans. Shorter protocol approximations based on standard uptake value ratios have been proposed. However, such methods depend on the time-point chosen for the quantification and often lead to overestimation and bias. The aim of this study was to develop a shorter protocol for the quantification of post-dose scans using a dual time-point approximation, which employs kinetic parameters from the baseline scan. Dual time-point was evaluated for a [11C]raclopride PET dose occupancy study with the D2 antagonist JNJ-37822681, obtaining estimates for binding potential and receptor occupancy. Results were compared to standard simplified reference tissue model and standard uptake value ratios-based estimates. Linear regression and Bland-Altman analysis demonstrated excellent correlation and agreement between dual time-point and the standard simplified reference tissue model approach. Moreover, the stability of dual time-point-based estimates is shown to be independent of the time-point chosen for quantification. Therefore, a dual time-point imaging protocol can be applied to post-dose [11C]raclopride PET scans, resulting in a significant reduction in total acquisition time while maintaining accuracy in the quantification of both the binding potential and the receptor occupancy.

Keywords: Dual time-point; [11C]raclopride; binding potential; positron emission tomography; quantification.

MeSH terms

  • Carbon Radioisotopes
  • Clinical Protocols
  • Dopamine D2 Receptor Antagonists / metabolism
  • Humans
  • Piperidines / analysis*
  • Piperidines / metabolism
  • Positron-Emission Tomography / methods*
  • Positron-Emission Tomography / standards
  • Protein Binding
  • Pyridazines / analysis*
  • Pyridazines / metabolism
  • Raclopride / analysis*
  • Raclopride / metabolism
  • Radionuclide Imaging / methods
  • Radionuclide Imaging / standards
  • Radiopharmaceuticals

Substances

  • Carbon Radioisotopes
  • Dopamine D2 Receptor Antagonists
  • N-(1-(3,4-difluorobenzyl)piperidin-4-yl)-6-(trifluoromethyl)pyridazin-3-amine
  • Piperidines
  • Pyridazines
  • Radiopharmaceuticals
  • Raclopride