Development of Generator Produced Positron Emitting Radionuclide Containing Diagnostic Radiopharmaceutical

为促进定位核医学的发展，重点建立定位放射金属核素（P-RI）的发生器生产系统，开发用于肿瘤和脑、心疾病诊断的P-RI标记药物。最初，62-Cu, 68-M， 82-Rb和52m-Mn发生器引起了我们的兴趣，但是，根据国际上的进展，1)62-Cu发生器系统，2)62-Cu和3)68-Ga标记诊断试剂的发展占据了更紧迫的地位。在此基础上，取得了以下成果：1)62-Cu发生器系统的生产：首先以天然铜为靶进行了63-Cu (p, 2n) 62-Zn核反应；然后，对62-Cu子元素与62-Zn母元素的分离方法进行了研究。通过对各种分析条件的研究，将产物洗脱为62- ci -甘氨酸配合物，实现了一套实用的生成系统，为生产高纯度、高产率的62-Cu提供了基础。2) 62-Cu标记的诊断剂：基于二硫代氨基脲（DTS）与62-Cu形成高度稳定、致密、不变的配合物的能力，利用该分子设计双功能螯合剂，如62-Cu标记白蛋白、62-Cu标记长链脂肪酸（心肌代谢功能诊断）、62-Cu-DTS-esther衍生物（脑血流诊断）。然后，根据其未来临床适用性的基本要求，评估每种开发的药物在目标组织或器官中的蓄积机制。3) 68-Ga标记诊断剂：放射性标记68-Ga-柠檬酸盐在核医学中用于肿瘤诊断需要一些基础研究，使其在短半衰期内特异性积累。此外，68-Ga标记的肿瘤抗体在核医学中的应用也在进行一些体外和体内研究。总之，每个结果都为未来的发展指明了道路。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