Vol.:(0123456789) 1 3 Ann Nucl Med (2017) 31:273–282 DOI 10.1007/s12149-017-1155-6 ORIGINAL ARTICLE Visual evaluation of kinetic characteristics of PET probe for neuroreceptors using a two-phase graphic plot analysis Hiroshi Ito 1,2  · Yoko Ikoma 3  · Chie Seki 1  · Yasuyuki Kimura 1  · Hiroshi Kawaguchi 3,4  · Hiroyuki Takuwa 1  · Masanori Ichise 1  · Tetsuya Suhara 1  · Iwao Kanno 1   Received: 25 October 2016 / Accepted: 16 January 2017 / Published online: 8 February 2017 © The Japanese Society of Nuclear Medicine 2017 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 specifc binding and slower dissocia- tion of specifc binding. The quartile deviations of V ND and BP ND determined by kinetic analysis were smaller for radi- oligands with slow dissociation. Conclusions The larger curvature of graphic plots for radioligands with slow dis- sociation might indicate a stable determination of V ND and BP ND by kinetic analysis. For investigation of the kinet- ics of radioligands, such kinetic characteristics should be considered. Keywords PET · Graphic plot analysis · Receptor · Transporter Introduction In positron emission tomography (PET) studies with radio- ligands for neuroreceptors and transporters, tracer kinetics have been described by the standard two-tissue compart- ment model with four frst-order rate constants contain- ing the compartments of non-displaceable binding and specifc binding to receptors or transporters [1–3]. The rate constants can be determined by a conventional non- linear curve-ftting procedure in a least-squares sense, and the binding potential corresponding to specifc binding to receptors or transporters is calculated from these rate con- stants. The binding characteristics of radioligands in brain Abstract Objectives In PET studies for neuroreceptors, tracer kinetics are described by the two-tissue compart- ment model (2-TCM), and binding parameters, including the total distribution volume (V T ), non-displaceable distri- bution volume (V ND ), and binding potential (BP ND ), 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 devel- oped a two-phase graphic plot analysis in which V ND and V T can 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 neurorecep- tors, 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 bind- ing parameters. Methods 90-min TACs were generated with the arterial input function and assumed kinetic parameters * Yoko Ikoma ikoma.yoko@qst.go.jp 1 Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan 2 Department of Radiology and Nuclear Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan 3 Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan 4 Human Informatics Research Institute, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8561, Japan