Development of Generator Produced Positron Emitting Radionuclide Containing Diagnostic Radiopharmaceutical

为促进阵地核医学的发展，我们的重点是建立阵地发射金属放射性核素(P-RI)产生器生产系统，开发用于肿瘤和脑、心脏疾病诊断的P-RI标记药物。起初，62-铜、68-M、82-Rb和52M-Mn发生器引起了我们的兴趣，但根据国际上的进展，1)62-铜发生器系统，2)62-铜和3)68-Ga标记诊断试剂的开发占据了更紧迫的位置。1)62-铜发生系统的研制：首先，以天然铜为靶进行了63-Cu(p，2n)62-Zn核反应，然后研究了62-Cu子体与62-Zn母体的分离方法。在研究了各种分析条件后，将女儿作为62-Ci-甘氨酸络合物洗脱，从而实现了实用的发生器SY…2)62-铜标记诊断剂：基于二硫代氨基脲(DTS)与62-铜形成高度稳定、致密且不变的络合物的能力，该分子被用于设计双功能螯合剂，如62-铜标记的白蛋白、62-铜标记的长链脂肪酸(心肌代谢功能诊断)、62-铜-DTS-Esther衍生物(脑血流诊断)。然后，根据未来临床应用所需的基本要求，评估每个已开发的试剂在感兴趣的组织或器官中的蓄积机制。3)68-Ga标记的诊断剂：在核医学中使用放射性标记的68-Ga-柠檬酸盐进行肿瘤诊断需要进行一些基础研究，使其能够在短的半衰期内特异性蓄积。此外，一些关于68-Ga标记的肿瘤抗体在核医学中合理使用的体外和体内研究正在进行中。总而言之，每个结果都为未来的发展设定了道路。较少

To promote the expansion of Position Nuclear Medicine,our attention was focused in the establishment of generator production system for position emitting radiometallic nuclide (P-RI) and in the development of P-RI labeled pharmaceuticals for the diagnosis of tumor and brain, heart disorders . At first, 62-Cu, 68-M, 82-Rb and 52m-Mn generators attracted our interest, however, according to progress in the international arena, the development of 1) 62-Cu generator system, 2) 62-Cu and 3) 68-Ga labeled diagnostic agents occupies more imminent place. On those basis, the results are described below as follows:1) Production of 62-Cu generator system : at first, the 63-Cu (p, 2n) 62-Zn nuclear reaction using natural copper as the target was carried out; then, a separation methodology for the 62-Cu daughter from its 62-Zn parent was surveyed. After studying various analytical conditions, the elution of the daughter as the 62-Ci-glycine complex enabled the achievement of a practical generator sy … More stem for the production of of 62-Cu with high purity and high yield.2) 62-Cu labeled diagnostic agent: based on the ability of dithiosemicarbazone (DTS) to render highly stable, compact and unchanged complex with 62-Cu, this molecule was used for the design of bifunctional chelating agents, such as, the 62-Cu labeled albumin, 62-Cu labeled long chain fatty acids (function diagnosis of myocardium metabolism), 62-Cu-DTS-esther derivatives (cerebral blood flow diagnosis). Then, the accumulation mechanism of each developed agent in the tissue or organ of interest was evaluated according, to the basic,requirement needed for their future clinical applicability.3) 68-Ga labeled diagnostic agent: the use of radiolabeled 68-Ga-citrate for the tumor diagnosis in Nuclear Medicine calls for some basic studies enabling its specific accumulation within the short half-life. Also, some in-vitro and in-vivo studies with 68-Ga labeled tumor antibodies for its plausible use in Nuclear medicine is under progress.In conclusion, each result set together the pathway for future development. Less