Visual evaluation of kinetic characteristics of PET probe for neuroreceptors using a two-phase graphic plot analysis.
Objectives In PET studies for neuroreceptors, tracer kinetics are described by the two-tissue compartment model (2-TCM), and binding parameters, including the total distribution volume (VT), non-displaceable distribution volume (VND), and binding potential (BPND), can be determined from model parameters estimated by kinetic analysis. The stability of binding parameter estimates depends on the kinetic characteristics of radioligands. To describe these kinetic characteristics, we previously developed a two-phase graphic plot analysis in which VNDand VTcan be estimated from the x-intercept of regression lines for early and delayed phases, respectively. In this study, we applied this graphic plot analysis to visual evaluation of the kinetic characteristics of radioligands for neuroreceptors, and investigated a relationship between the shape of these graphic plots and the stability of binding parameters estimated by the kinetic analysis with 2-TCM in simulated brain tissue time-activity curves (TACs) with various binding parameters. Methods 90-min TACs were generated with the arterial input function and assumed kinetic parameters according to 2-TCM. Graphic plot analysis was applied to these simulated TACs, and the curvature of the plot for each TAC was evaluated visually. TACs with several noise levels were also generated with various kinetic parameters, and the bias and variation of binding parameters estimated by kinetic analysis were calculated in each TAC. These bias and variation were compared with the shape of graphic plots. Results The graphic plots showed larger curvature for TACs with higher specific binding and slower dissociation of specific binding. The quartile deviations of VNDand BPNDdetermined by kinetic analysis were smaller for radioligands with slow dissociation. Conclusions The larger curvature of graphic plots for radioligands with slow dissociation might indicate a stable determination of VNDand BPNDby kinetic analysis. For investigation of the kinetics of radioligands, such kinetic characteristics should be considered.
Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.|Department of Radiology and Nuclear Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Hiroshi
H
Ito
Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. ikoma.yoko@qst.go.jp.
Yoko
Y
Ikoma
Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Chie
C
Seki
Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Yasuyuki
Y
Kimura
Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.|Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8561, Japan.
Hiroshi
H
Kawaguchi
Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Hiroyuki
H
Takuwa
Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Masanori
M
Ichise
Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Tetsuya
T
Suhara
Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Iwao
I
Kanno
D000081:Acetamides / Q000493:pharmacokinetics; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D016018:Least-Squares Analysis; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009288:Naproxen / Q000493:pharmacokinetics; D010647:Phenyl Ethers / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011984:Sensory Receptor Cells / Q000378:metabolism*
D000081:Acetamides; D002250:Carbon Radioisotopes; C118942:DAA 1106; D010647:Phenyl Ethers; D019275:Radiopharmaceuticals; D009288:Naproxen
Graphic plot analysis; PET; Receptor; Transporter