DEVELOPMENT OF 99M-TC BRAIN IMAGING AGENTS

99M-TC脑显像剂的开发

• 批准号: 3183095
• 负责人: EDWARD A DEUTSCH
• 金额: $ 13.43万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 1990-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183095
• 关键词: blood brain barrier; carbon dioxide tension; contrast media; ligands; oxidation reduction reaction; passive transport; radiopharmacology; radiotracer; single photon emission computed tomography; technetium

The primary objective of this research is the development of neutral, lipophilic 99m-Tc agents that will be useful for monitoring regional cerebral blood flow by SPECT (single photon emission computed tomography). This will be accomplished by merging the techniques and expertise of inorganic chemistry with those of nuclear medicine. Important steps in this process include the following: (1) The sysntheis and characterization of new technetium complexes, using first macroscopic amounts of 99-Tc so that chemical characterizations can be accomplished, and then "no carrier added" 99m-Tc for the preparation of radiopharmaceuticals. Characterizations of new complexes will depend heavily on single crystal x-ray structural analysis, electrochemical analysis, and HPLC (high performance liquid chromatography). (2) The development of the brain imaging agents that function by a "redox trapping" mechanism wherin oxidation in the brain converts neutral molecules into cations which cannot diffuse back out across the blood-brain barrier. Such agents will be based on complexes in which the technetium center is itself redox active, and on complexes in which the redox active site is a dihydropyridine moeity. (3) The elucidation of the biologrical mechanism of action of existing 99m-Tc brain imaging agents which contain Tc(V) centers. Experiments will be conducted to probe the interactions that can occure between the biological milieu and the oxo-Tc(V) core, the Tc center itself, and the organic ligand used to generate the 99M-Tc(V) radioparmaceutical. (4) Comparison of the clinical utility and efficacy of 123-I-IMP and 99m-Tc-HMPAO (IMP = N-isoproply-p-iodoamphetamine; HMPAO = hexamethylpropylene amine oxime), two agents which must act by different biological mechanisms. These studies will employ qualitative and quantitative SPECT imaging techniques, tramsmission computed tomography, and, in selected cases, the 133-Xe washout technique. Subjects will include normal volunteers and patients with one of the following diagnoses: (i) transient ischemic attack (TIA), (ii) cerebrovascular accident, (iii) primary or metastatic tumor, (iv) idiopathic seizure disorder. (5) Comparison of the clinical utility and efficacy of 99-m-Tc-HMPAO and new 99m-Tc brain imaging radiopharmaceuticals, especially those that utilize the "redox trapping" mechanism. These studied will further delineate the qualitative and quantitative manifestations resulting from the use of agents that function by different biological mechanisms. (6) Evaluation of CO2 stress as a means of enhancing detection of abnormal regional cerebral blood flow in patients with TIA. The studies will evaluate both the clinical utility of the techinique, and the relative efficacy of different radiopharmaceuticals used with the technique.

本研究的主要目标是开发中性， 亲脂性99 m-Tc试剂，将用于监测区域 脑血流SPECT（单光子发射计算机断层扫描）。 这将通过合并技术和专业知识来实现， 无机化学与核医学的关系。 的重要步骤 （1）合成与表征 新的锝配合物，使用第一个宏观量的99-Tc， 可以完成化学表征，然后“没有载体 增加了”99 m-Tc用于制备放射性药物。 新配合物的表征将在很大程度上依赖于单晶 X射线结构分析、电化学分析和HPLC（高 高效液相色谱法）。 (2)大脑的发育 通过“氧化还原捕获”机制起作用的成像剂， 大脑中的氧化将中性分子转化为阳离子， 扩散回血脑屏障 这些代理将基于 在络合物中，锝中心本身具有氧化还原活性， 络合物，其中氧化还原活性位点是二氢吡啶部分。 （三） 现有~（99）m-Tc的生物学作用机制的阐明 含有Tc（V）中心的脑成像剂。 实验将 进行了探测生物之间可能发生的相互作用， 环境和氧代-Tc（V）核心、Tc中心本身和有机配体 用于生成99 M-Tc（V）放射性参数。 (4)比较 123-I-IMP和99 m-Tc-HMPAO的临床应用和疗效（IMP = N-异丙基-p-碘苯丙胺; HMPAO =六甲基丙烯胺肟）， 这两种物质必须通过不同的生物机制起作用。 这些 研究将采用定性和定量SPECT成像技术， 透射式计算机断层扫描，并在选定的情况下，133-溴化乙锭 洗脱技术 受试者将包括正常志愿者和患者 具有以下诊断之一：（i）短暂性脑缺血发作（TIA）， (ii)脑血管意外，（iii）原发性或转移性肿瘤，（iv） 特发性癫痫 (5)临床实用性比较， 99-m-Tc-HMPAO和新99-m-Tc脑显像的有效性 放射性药物，特别是那些利用“氧化还原捕获” 机制 这些研究将进一步描述定性和 由于使用具有功能的试剂而导致的定量表现 不同的生物机制。 (6)CO2胁迫作为一种 增强局部脑血流异常检测的方法 TIA患者。 这些研究将评估 不同放射性药物的技术和相对功效 使用该技术。