Technetium and Rhenium in Nuclear Medicine

描述（由申请人提供）：本提案中描述的研究是基于99 mTc仍将是常规临床核医学实践中重要放射性核素这一前提的项目的继续。主要的推动力是在两个领域开发新的药物，再加上一些精心挑选的化学研究，旨在增加产品复合物设计的灵活性，从而增加其生物学行为。第一个主要目标是继续评价能够检测体内恶性黑色素瘤存在的锝络合物。在当前的周期中，已经确定了几种潜在的候选物在黑色素瘤的动物模型中显示出显著的摄取，包括转移性扩散到肺部的一种。一种新的高分辨率microSPECT相机现在已经使纵向研究成为可能，可以监测肿瘤随时间的生长，这是一种非常有用的能力，将在拟议期间进一步追求。第二个主要目标是继续设计对5 HT 1A受体具有亲和力的复合物。在过去的几年里，人们越来越清楚地认识到，除了在中枢神经系统中的既定功能外，神经递质系统在癌症在人体内的生长和扩散中发挥着重要作用。因此，计划在正常脑和前列腺癌的体内模型中测定摄取，前列腺癌是表达这种受体类型的肿瘤的实例。寻找对5-HT 1A受体具有高亲和性和选择性的复合物具有重要的意义，其研究具有重要的双重目的的前景。第三个主要目的是检查两种金属核作为目的1和2中使用的Tc/Re（V）氧代核的替代物的化学行为和配体偏好：相对充分研究的Tc（I）三羰基核和较少探索的Tc（I）亚硝酰基核。将进行该化学反应以支持目标1和2中的工作，因为目标1和2中的核心应在用于安装给定生物活性部分的最终平台的设计中提供更大的灵活性。恶性黑色素瘤和前列腺癌都是这个国家严重的公共卫生问题。这项工作的目的是开发一种手段，检测这些肿瘤在临床上使用非侵入性成像技术。小动物模型的microSPECT成像能力也可以证明在临床前研究中评估这些疾病的新疗法的发展是有用的。

DESCRIPTION (provided by applicant): The research described in this proposal is the continuation of a program based on the premise that 99mTc will remain an important radionuclide in the practice of routine clinical nuclear medicine. The primary thrust is the development of new agents in two areas, coupled with some carefully selected chemical studies intended to add flexibility in the design of the product complexes and, thus, their biologic behavior. The first major aim is to continue the evaluation of technetium complexes capable of detecting the presence of malignant melanoma in vivo. Over this current cycle, several potential candidates have been identified as showing significant uptake in animal models of melanoma, including one of metastatic spread to the lungs. A new high resolution microSPECT camera has now made possible longitudinal studies that allow monitoring of tumor growth with time, a highly useful capability that will be pursued further in the proposed period. The second major aim is to continue designing complexes that have affinity for the 5HT1A receptor. Over the past few years it has become increasingly clear that, apart from their established function in the central nervous system, neurotransmitter systems play a significant role in the growth and spread of cancer throughout the human body. Thus, it is planned to assay uptake in both normal brain and in vivo models of prostate cancer, an example of tumors that express this receptor type. The search for complexes with high affinity and selectivity for 5HT1A receptors increases in importance with the prospect of important dual purposes for the research. The third major aim is to examine the chemical behavior and ligand preferences of two metal cores as alternatives to the Tc/Re(V) oxo core used in aims 1 and 2: the relatively well-studied Tc(l) tricarbonyl core and the less well-explored Tc(l) nitrosyl core. This chemistry will be conducted in support of the work in aims 1 and 2 in that the latter cores should provide more flexibility in the design of the final platform for mounting a given biologically active moiety. Malignant melanoma and prostate cancer are both serious public health problems in this country. This work is designed to develop a means of detecting these tumors in the clinic using noninvasive imaging techniques. The microSPECT imaging capability with small-animal models could also prove useful in preclinical studies assessing the development of new therapies for these diseases.