title: Dual time-point imaging for post-dose binding potential estimation applied to a [11C]raclopride PET dose occupancy study.
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.
authors.affiliation: 1 Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Isadora
authors.initials: I
authors.lastname: Lopes Alves
authors.affiliation: 1 Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Antoon Tm
authors.initials: AT
authors.lastname: Willemsen
authors.affiliation: 1 Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudi A
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: 2 Laboratory of Medical Imaging, School of Physics, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Ana Maria M
authors.initials: AM
authors.lastname: da Silva
authors.affiliation: 1 Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|3 Department of Nuclear Medicine and Molecular Imaging, KU Leuven, Leuven, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
mesh_terms: D002250:Carbon Radioisotopes; D002985:Clinical Protocols; D065127:Dopamine D2 Receptor Antagonists / Q000378:metabolism; D006801:Humans; D010880:Piperidines / Q000032:analysis* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards; D011485:Protein Binding; D011724:Pyridazines / Q000032:analysis* / Q000378:metabolism; D020891:Raclopride / Q000032:analysis* / Q000378:metabolism; D011877:Radionuclide Imaging / Q000379:methods / Q000592:standards; D019275:Radiopharmaceuticals
chemical_list: D002250:Carbon Radioisotopes; D065127:Dopamine D2 Receptor Antagonists; C576398:N-(1-(3,4-difluorobenzyl)piperidin-4-yl)-6-(trifluoromethyl)pyridazin-3-amine; D010880:Piperidines; D011724:Pyridazines; D019275:Radiopharmaceuticals; D020891:Raclopride
keywords: Dual time-point; [11C]raclopride; binding potential; positron emission tomography; quantification