Retest imaging of [11C]NOP-1A binding to nociceptin/orphanin FQ peptide (NOP) receptors in the brain of healthy humans.
[(11)C]NOP-1A is a novel high-affinity PET ligand for imaging nociceptin/orphanin FQ peptide (NOP) receptors. Here, we report reproducibility and reliability measures of binding parameter estimates for [(11)C]NOP-1A binding in the brain of healthy humans. After intravenous injection of [(11)C]NOP-1A, PET scans were conducted twice on eleven healthy volunteers on the same (10/11 subjects) or different (1/11 subjects) days. Subjects underwent serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (VT; a measure of receptor density) was determined by compartmental (one- and two-tissue) modeling in large regions and by simpler regression methods (graphical Logan and bilinear MA1) in both large regions and voxel data. Retest variability and intraclass correlation coefficient (ICC) of VT were determined as measures of reproducibility and reliability respectively. Regional [(11)C]NOP-1A uptake in the brain was high, with a peak radioactivity concentration of 4-7 SUV (standardized uptake value) and a rank order of putamen>cingulate cortex>cerebellum. Brain time-activity curves fitted well in 10 of 11 subjects by unconstrained two-tissue compartmental model. The retest variability of VT was moderately good across brain regions except cerebellum, and was similar across different modeling methods, averaging 12% for large regions and 14% for voxel-based methods. The retest reliability of VT was also moderately good in most brain regions, except thalamus and cerebellum, and was similar across different modeling methods averaging 0.46 for large regions and 0.48 for voxels having gray matter probability >20%. The lowest retest variability and highest retest reliability of VT were achieved by compartmental modeling for large regions, and by the parametric Logan method for voxel-based methods. Moderately good reproducibility and reliability measures of VT for [(11)C]NOP-1A make it a useful PET ligand for comparing NOP receptor binding between different subject groups or under different conditions in the same subject.
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: lohithhere@gmail.com.
Talakad G
TG
Lohith
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Sami S
SS
Zoghbi
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Cheryl L
CL
Morse
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Maria D Ferraris
MD
Araneta
Eli Lilly & Co., Indianapolis, IN, USA.
Vanessa N
VN
Barth
Eli Lilly & Co., Indianapolis, IN, USA.
Nancy A
NA
Goebl
Eli Lilly & Co., Indianapolis, IN, USA.
Johannes T
JT
Tauscher
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Victor W
VW
Pike
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: robert.innis@nih.gov.
Robert B
RB
Innis
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Masahiro
M
Fujita
D000328:Adult; D019540:Area Under Curve; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D018847:Opioid Peptides / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011957:Receptors, Opioid / Q000032:analysis* / Q000378:metabolism; D015203:Reproducibility of Results; D055815:Young Adult; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002250:Carbon Radioisotopes; D018847:Opioid Peptides; D019275:Radiopharmaceuticals; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human
AUC; BSMSS; ICC; NOP; NOP receptors; Nociceptin; PET; Test–retest imaging; V(T); WSMSS; area-under-the-curve; between-subject mean sum of squares; f(P); intraclass correlation coefficient; nociceptin/orphanin FQ peptide; plasma free fraction; positron emission tomography; retest variability; total distribution volume; within-subject mean sum of squares