@misc{oai:repo.qst.go.jp:00070846,
 author = {Seki, Chie and Tokunaga, Masaki and Hattori, Satoko and Maruyama, Masahiro and Ono, Maiko and Ki, Hin and Maeda, Jun and Suhara, Tetsuya and Higuchi, Makoto and Ito, Hiroshi and 関 千江 and 徳永 正希 and 服部 聡子 and 丸山 将浩 and 小野 麻衣子 and 季 斌 and 前田 純 and 須原 哲也 and 樋口 真人 and 伊藤 浩},
 month = {Aug},
 note = {Introduction 
[11C]PIB is a widely-used PET ligand to evaluate amyloid beta (Abeta) deposition in vivo. Although the nature of its binding properties is yet to be clarified, detailed quantitative PET assays of living animal models may provide critical insights into the molecular basis of the radioligand kinetics. We performed dynamic PET scans simultaneously with measurement of metabolite-corrected arterial input function (pTAC) to obtain kinetic parameters in two different types of amyloid precursor protein (APP) transgenic (Tg) and wild-type (WT) mice. APP23 Tg mice mainly develop dense-cored cortical and hippocampal Abeta plaques, while APP-SL Tg mice exhibit cerebrovascular and leptomenigeal Abeta deposition (cerebral amyloid angiopathy, CAA) with only a small number of parenchymal plaques. Regional kinetic parameters for [11C]PIB were compared with postmortem plaque staining in the same individuals to investigate association of these parameters with amounts and types of  Abeta deposits. 
Methods 
APP23 Tg (4 females at 24-26 mo), APP-SL Tg (1 male and 1 female at 23-24 mo), and WT (1 male and 3 females at 24-26 mo) mice were used. Immediately after intravenous injection of [11C]PIB (38+/-13 MBq, 106+/-60 GBq/micro-mol), 60-min PET data acquisition with MicroPET focus 220 and serial arterial blood sampling were conducted. Regional brain time-activity curves (tTACs) were obtained from dynamic PET data with the aid of structural MR images. pTAC was obtained from radioactivity concentration and parent radioligand fraction in the plasma. Two-tissue compartment model analysis was then performed to estimate kinetic parameters (K1-k4) and total volume of distribution (VT) for the radioligand. Distribution volume ratio (DVR) was also calculated using the pons as reference region, because abundant CAA in the cerebellum of APP-SL mice hampered the use of cerebellar data as reference, and because estimated VT values in the pons were similar among Tg and WT mice. Mouse brains were removed after PET scans, fixed with 4% paraformaldehyde, cryoprotected in 30% sucrose, and sectioned coronally, followed by staining with 0.01% (E,E)1-fluoro-2,5-bis(3-carboxy-4-hydroxystyryl)benzene (FSB), an amyloid- binding fluorescent dye. 
Results and Conclusion 
k3/k4, VT and DVR in the neocortex and hippocampus of APP23 Tg mice were higher than those of WT mice, and the increase of these parameters was correlated with the density of FSB-stained parenchymal Abeta deposits. DVR showed small intragroup variability compared to k3/k4 and VT, and is accordingly useful as a robust measure of plaque formation. k4 values of these regions in APP23 Tg mice were significantly lower than other regions lacking notable plaque deposition, while no plaque-related changes of k3 values were observed. These data suggest that plaques in APP23 Tg mice contain high-affinity but low-capacity binding components relative to nonspecific binding sites. VT and DVR values in the cerebellum of APP-SL Tg mice were higher than those of APP23 Tg and WT mice, presumably reflecting accumulation of CAA in this area. In summary, the present study supports the utility of Tg mice and small-animal PET system for validation of quantitative analytical methods by assessing correlations between kinetic parameter estimates and pathological changes., The 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain (NRM2012)},
 title = {Relationship between kinetic parameters of [11C]PIB and amyloid bata deposition studied in amyloid precursor protein transgenic mouse brains},
 year = {2012}
}