Kinetic modeling of the serotonin 5-HT(1B) receptor radioligand [(11)C]P943 in humans.
[(11)C]P943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT(1B)) receptors with positron emission tomography (PET). The purpose of this study was to evaluate [(11)C]P943 for this application in humans, and to determine the most suitable quantification method. Positron emission tomography data and arterial input function measurements were acquired in a cohort of 32 human subjects. Using arterial input functions, compartmental modeling, the Logan graphical analysis, and the multilinear method MA1 were tested. Both the two tissue-compartment model and MA1 provided good fits of the PET data and reliable distribution volume estimates. Using the cerebellum as a reference region, BP(ND) binding potential estimates were computed. [(11)C]P943 BP(ND) estimates were significantly correlated with in vitro measurements of the density of 5-HT(1B) receptors, with highest values in the occipital cortex and pallidum. To evaluate noninvasive methods, two- and three-parameter graphical analyses, Simplified Reference Tissue Models (SRTM and SRTM2), and Multilinear Reference Tissue Models (MRTM and MRTM2) were tested. The MRTM2 model provided the best correlation with MA1 binding-potential estimates. Parametric images of the volume of distribution or binding potential of [(11)C]P943 could be computed using both MA1 and MRTM2. The results show that [(11)C]P943 provides quantitative measurements of 5-HT(1B) binding potential.
PET Center, Department of Diagnostic Radiology, Yale University, New Haven, Connecticut, USA. jean-dominique.gallezot@yale.edu
Jean-Dominique
JD
Gallezot
Nabeel
N
Nabulsi
Alexander
A
Neumeister
Beata
B
Planeta-Wilson
Wendol A
WA
Williams
Tarun
T
Singhal
Sunhee
S
Kim
R Paul
RP
Maguire
Timothy
T
McCarthy
J James
JJ
Frost
Yiyun
Y
Huang
Yu-Shin
YS
Ding
Richard E
RE
Carson
D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D001523:Mental Disorders / Q000000981:diagnostic imaging / Q000378:metabolism; D015233:Models, Statistical; D010879:Piperazines / Q000138:chemical synthesis; D049268:Positron-Emission Tomography; D011760:Pyrrolidinones / Q000138:chemical synthesis; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*
C546827:1-(4-(2-methoxyisopropyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)benzyl)pyrrolidin-2-one; D010879:Piperazines; D011760:Pyrrolidinones; D019275:Radiopharmaceuticals; D044302:Receptor, Serotonin, 5-HT1B