TECHNETIUM AND RHENIUM IN NUCLEAR MEDICINE

描述(改编自申请者摘要)：放射性核素 ~(99m)Tm继续是常规临床核的中流砥柱 医药。这项研究计划最初是在以下前提下构思的 这种放射性核素在诊断中的有用性只能通过 对元素的基础化学进行严格研究，并 将这一知识纳入到新放射性药物的设计中。这 同样适用于基于放射性核素的治疗应用 它的同系物Re。在接下来的时间里，申请者提议 主要集中在两大化学领域：低价化学 氧化态(1)和(2)，包括对络合物的继续研究 弱场配体，可提供生成新类化合物的途径 水介质中来自常规前驱体的络合物，如高铁酸盐 离子：以及有机肼化学，这是一个高度复杂的领域，已经开始 用于某些放射性药物应用，例如，螯合物 6-肼烟酰胺(HYNIC)。在化学应用方面，这项工作 将包括对单胺-单胺二硫醇(MAMA或AAST)的研究 共轭配体靶向于大脑中的5HT-1a受体。因素 影响局部化的因素，如结构、螯合物亲脂性的选择、 该络合物在生理条件下的pKa，以及对 其他受体类型将被研究。并行地，一种固态合成方法 生产高比活度的氚络合物样品 将探索受体靶向。这在以下情况下是至关重要的 未标记的前体配体可以与最终的络合物竞争结合部位 职业。应用程序中的最后一部分将集中在肿瘤方面 侦测。首先，为研究大脑而开发的5HT-1A配体将是 对它们检测神经内分泌介导的癌症的能力进行评估 前列腺。第二，正在建立一个研究小分子的计划 癌症的检测，首先使用共轭类似物 已经被其他人证明被热衷于购买的含碘化合物 黑色素瘤细胞。

DESCRIPTION (Adapted from Applicant's Abstract): The radionuclide technetium-99m continues to be the mainstay of routine clinical nuclear medicine. This research program was originally conceived on the premise that the usefulness of this radionuclide in diagnosis can only be maintained by conducting a rigorous study of the basic chemistry of the element and incorporating this knowledge into the design of new radiopharmaceuticals. This is equally true of therapeutic applications based on the use of radionuclides of its congener rhenium. In this next period the applicants proposed to concentrate primarily on two broad areas of chemistry: low valent chemistry in oxidation states (+1) and (+2), including the study of complexes continuing weak-field ligands that may provide routes into the production of new classes of complexes in aqueous media from routine precursors such as pertechnetate ion: and organohydrazine chemistry, a highly complex area that has begun to be used in certain radiopharmaceutical applications, for example, the chelate 6-hydrazinonicotinamide (HYNIC). In applications of the chemistry, the work will include an investigation of monoamide-monoamine bisthiol (MAMA or AAST) conjugated ligands targeted to 5HT-1A receptors in the brain. Factors affecting localization such as structure, choice of chelate lipophilicity, the pKa of the complex under physiological conditions, and selectivity against other receptor types will be studied. In parallel, a solid state synthesis for producing high-specific-activity samples of technetium complexes designed for receptor targeting will be explored. This is vital in circumstances where unlabeled precursor ligand could compete with the final complex for sites of occupation. The last section among the applications will focus on tumor detection. First, the 5HT-1A ligands developed for studying the brain will be evaluated for their ability to detect neuroendocrine mediated cancer of the prostate. Second, a program is being established to study small-molecule detection of cancer, in the first instance using conjugated analogs of iodinated compounds that have already bee shown by others to be avidly taken up by melanoma cells.