Technetium and Rhenium in Nuclear Medicine

核医学中的锝和铼

• 批准号: 7342139
• 负责人: Alun Gareth Jones
• 金额: $ 56.39万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-02-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342139
• 关键词: Affinity; Animal Model; Area; Behavior; Biological Assay; Brain; Budgets; Cells; Chemicals; Chemistry; Clinic; Clinical; Complex; Country; Coupled; Detection; Development; Discipline of Nuclear Medicine; Disease; Drug Kinetics; Evaluation; Faculty; Funding; Future; Grant; Growth; Human body; Image; Imaging Techniques; Inorganic Chemistry; Institutes; Intention; Lead; Ligands; Longitudinal Studies; Lung; Malignant Neoplasms; Malignant neoplasm of prostate; Massachusetts; Metals; Monitor; Neuraxis; Neurotransmitters; New Agents; Oxidation-Reduction; Pharmacodynamics; Play; Pliability; Public Health; Purpose; Radioisotopes; Radiopharmaceuticals; Research; Research Personnel; Resolution; Resources; Rhenium; Role; Sensory Receptors; Site; Source; Structure-Activity Relationship; System; Technetium; Technology; Time; Tissues; Work; base; cancer imaging; design; improved; in vivo; in vivo Model; medical schools; melanoma; oncology; pharmacophore; preclinical study; preference; programs; receptor; single photon emission computed tomography; tertiary amine; tumor; tumor growth; uptake

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 1and 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.

本提案中描述的研究是基于99 mTc 在常规临床核医学实践中仍将是重要的放射性核素。主要的推力是 在两个领域开发新的制剂，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 主要目的是继续评估能够检测存在的锝络合物， 体内恶性黑素瘤。在本周期内，已确定若干潜在候选人， 在黑色素瘤动物模型中显示出显著的摄取，包括转移性扩散到肺的黑色素瘤。一 新型高分辨率microSPECT相机现已实现纵向研究，从而实现监测 这是一项非常有用的能力，将在拟议期间进一步研究。的 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。来 在过去几年中，人们越来越清楚地看到，除了在中央政府中的既定职能外， 神经系统、神经递质系统在癌症的生长和扩散中起着重要作用 在整个人体内。因此，计划测定正常脑和体内模型中的摄取， 前列腺癌，表达这种受体类型的肿瘤的一个例子。寻找高分子配合物 对5-HT 1A受体的亲和性和选择性随着重要的双重靶向治疗的前景而增加。 研究目的。第三个主要目的是检查化学行为和配体偏好 两种金属核作为目标1和2中使用的Tc/Re（V）氧代核的替代品： Tc（I）三羰基核心和较少研究的Tc（I）亚硝酰基核心。这种化学反应将在 支持目标1和目标2的工作，因为目标2的核心应在目标1和目标2的设计方面提供更大的灵活性。 用于安装给定生物活性部分的最终平台。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， 这些肿瘤在临床上使用非侵入性成像技术。microSPECT成像能力， 小动物模型也可以证明在临床前研究中评估新的 治疗这些疾病。