Research and Development of Apoptosis Detection by PET.

凋亡是细胞单位中的一种现象，凋亡成像的发展将有助于解决各种疾病的未知病理学，诊断和治疗决策。放射性核素核医学成像可能是对细胞凋亡等分子生物学现象进行成像的最敏感和最有可能的技术。在这些技术中，正电子发射断层扫描（PET）由于其高定量成像技术而受到关注。本研究在群马大学的PET设施中进行。本研究的目的是从基础和临床两个方面评价氨基酸转运蛋白标志物F-18 α甲基酪氨酸（FMT）和细胞膜磷脂代谢标志物C-11胆碱与细胞凋亡现象的关系。此外，我们还尝试开发新的C-11或F-18标记的PET示踪剂，在体内图像上检测属于磷脂家族的凋亡现象。因此，从临床数据分析中，我们无法发现FMT与C-11胆碱肿瘤摄取和凋亡现象之间的显著相关性。我们成功地生成了一个新的追踪器。C-11膜联蛋白，检测凋亡现象。C-11 Annexin对凋亡诱导细胞和未凋亡细胞的结合能力有显著差异，提示C-11 Annexin可作为检测凋亡细胞的一种新的示踪剂，在临床试验前需要进一步的动物实验研究。

Apoptotic death is a phenomenon in cellular unit, and the development of imaging the apoptotic death would be useful for resolving unknown pathophisiology of various disease, diagnoses, and therapeutic decision. The nuclear medicine imaging using radio nuclides might be the most sensitive and possible technology for imaging molecular biologic phenomenon such as apoptosis. In these technique, positron emission tomography (PET) has been focused because of its high quantitative imaging technology. This study was conducted in the PET facility in Gunma University. The aim of this study was to basically and clinically evaluate the relationship between the F-18 α methyltyrosine (FMT) as a amino-acid transporter marker, C-11 choline as a cellular membrane phospholipid metabolic marker and apoptotic phenomenon. Also we tried to develop new C-11 or F-18 labeled PET tracers detecting apoptotic phenomenon on in vivo images which were belonged to a phospholipids family. As a result, we could not find a significant correlation between FMT and C-11 choline tumor uptake and apoptotic phenomenon from clinical data analysis. We succeeded to generate a new tracer. C-11 Annexin, detecting apoptotic phenomenon. This new tracer showed a significant different cell biding ability between apoptosis free cells and apoptosis induced cells.C-11 Annexin appeared to be an arailable for detecting apoptotic cells and further investigation using in vivo animal study was warranted before clinical trials.