@misc{oai:repo.qst.go.jp:00069797,
 author = {Naganawa, Mika and Mishina, Masahiro and Sakata, Muneyuki and Oda, Keiichi and Ishii, Kenji and Ishiwata, Kiichi and Kimura, Yuichi and 長縄 美香 and 坂田 宗之 and 織田 圭一 and 石井 賢二 and 石渡 喜一 and 木村 裕一},
 month = {Jul},
 note = {Objectives: [11C]TMSX is one of the few available radioligands to quantify adenosine A2A receptor (A2AR) [1]. Although A2ARs are rich in the basal ganglia and poor in other regions, [11C]TMSX binds to not only classical A2ARs but also atypical sites. Therefore, it is difficult to find a reference region. In previous studies with arterial input function, we selected the centrum semiovale (CSO) as a reference region [2,3]. The purpose of this study was to investigate the availability of graphical analyses for human [11C]TMSX studies with region of interest (ROI) analysis.
\nMethods: Seven healthy subjects were included in this study. The average dose was 570 +- 86 MBq and the specific activity was 39 +- 21 GBq/µmol. Dynamic PET scans were acquired for 1 hour with a SET-2400W (Shimadzu, Japan). A total of 25 ROIs was manually delineated on the summed PET image: CSO (reference), anterior and posterior putamen, caudate, midbrain, posterior cingulate, cerebral cortical areas, and cerebellum. The regional time-activity curves (TACs) were analyzed using one- and two-tissue compartment models (1T, 2T), Logan graphical analysis (LGA) and multilinear analysis (MA1) with a metabolite-corrected input function. TACs were also analyzed using reference Logan graphical analysis (LGAR). The clearance rate constant of the reference region (k2') for LGAR was fixed to be 0.12 min-1, the mean value from the 1T model. For all graphical methods, t* was set to be 20 min post-injection.
\nResults: Metabolism of [11C]TMSX was very slow with parent fraction of 0.98 +- 0.01 at 3 min and 0.92 +- 0.05 at 60 min. The ROIs were well described by 2T model with a constraint of VND from the 1T estimation of CSO. The values of VT ranged from 0.58 +- 0.16 (CSO) to 1.25 +- 0.29 mL/cm3 (anterior putamen), with K1 values of 0.068 +- 0.014 to 0.30 +- 0.07 mL/min/cm3. The estimated VT of graphical analyses and 2T matched well (VT(LGA) = 0.99 VT(2T) + 0.01 (r2 = 0.99), VT(MA1) = 1.01 VT(2T) + 0.01 (r2 = 0.99)). The estimated VT in CSO was 5% higher in graphical analyses than in 1T model. As a result, the estimated BPND of LGA and MA1 showed smaller values compared with compartment model analysis (BPND(2T) = 0.83BPND(MA1) + 0.06 (r2 = 0.92)). The LGAR provided similar results (BPND(LGAR) = 0.99BPND(MA1) - 0.01 (r2 = 0.99)).
\nConclusions: All graphical analyses provided similar estimates of VT and BPND for ROI curves. This study suggests that LGAR is available for quantification of [11C]TMSX ROI analysis. The difference of BPND values in graphical analyses and compartment analysis is due to the estimates of VND value. The suitability of CSO as a reference region should be further investigated and the noise-reduction method is required for LGAR imaging.
\nReferences:
[1] Ishiwata K, et al. JNM, 41:345-354, 2000.
[2] Naganawa M, et al. EJNM, 34:679-687, 2007.
[3] Svenningsson P, et al. Synapse, 27:322-335, 1997.
Acknowledgments: This work was funded by Grants-in-Aid for Scientific Research (B) No. 16390348, (C) No. 17590901 and No. 20591033 from JSPS., Brain'09 & BrainPET'09},
 title = {Simplified Quantification of Adenosine A2A Receptor with [11C]TMSX PET and Graphical Analyses},
 year = {2009}
}