TECHNETIUM AND RHENIUM IN NUCLEAR MEDICINE

描述（改编自申请人的摘要）：放射性核素 锝-99m仍然是常规临床核试验的支柱。 药 这项研究计划最初的设想是在这样的前提下， 这种放射性核素在诊断中的有用性只能通过 对元素的基本化学进行严格的研究， 将这些知识整合到新放射性药物的设计中。 这 对于基于使用放射性核素的治疗应用同样如此 它的同类物 在下一个时期，申请人提出， 主要集中在两个广泛的化学领域：低价化学， 氧化态（+1）和（+2），包括继续研究络合物 弱场配体，可能提供新类别的生产路线 络合物在水介质中从常规前体， 离子：和有机肼化学，一个高度复杂的领域，已开始 用于某些放射性药物应用，例如，螯合物 6-肼基烟酰胺（HYNIC）。 在化学的应用中， 将包括对单酰胺-单胺双硫醇（MAMA或AAST）的研究 靶向脑中5 HT-1A受体的缀合配体。 因素 影响定位的因素，如结构、螯合亲脂性的选择、 在生理条件下的复合物的pKa，和对 将研究其它受体类型。 同时，进行了固态合成， 生产高比活度的锝络合物样品， 将探索受体靶向。 这在以下情况下至关重要： 未标记的前体配体可以与最终的复合物竞争 职业. 最后一节的应用程序将集中在肿瘤 侦测 首先，为研究大脑而开发的5 HT-1A配体将是 评估其检测神经内分泌介导的肿瘤的能力。 前列腺 第二，正在建立一个研究小分子 癌症的检测，在第一种情况下使用缀合的 碘化化合物已经被其他人证明是被贪婪地摄取 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.