DEVELOPMENT OF 99M-TC BRAIN IMAGING AGENTS FOR USE WITH

这项研究的主要目标是发展中性， 可用于区域监测的亲脂性99m-Tc试剂 脑血流SPECT(单光子发射计算机断层扫描)。 这将通过融合技术和专业知识来实现 无机化学与核医学。采取的重要步骤 这一过程包括以下几个方面：(1)合成和表征 使用第一宏观量的99TcSO 可以完成化学表征，然后“没有载体” 增加了“用于制备放射性药物的99m-Tc”。 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、电化学分析和高效液相色谱(High 高效液相色谱)。(2)大脑的发育 通过“氧化还原陷阱”机制起作用的显像剂 大脑中的氧化作用将中性分子转化为阳离子，而阳离子不能 扩散回血脑屏障。这些特工将驻扎在 关于氚中心本身是氧化还原活性的络合物，以及 氧化还原活性中心为二氢吡啶基团的配合物。(3) ~(99m)Tc存在的生物作用机制的阐明 含有Tc(V)中心的脑显像剂。实验将是 以探索生物与生物之间可能发生的相互作用 环境和氧代-TC(V)核、TC中心本身和有机配体 用于生产99m-Tc(V)放射性核素。(4)中美之间的比较 123-I-IMP和99m-Tc-HMPAO的临床应用和疗效(IMP= N-异丙基对碘苯丙胺；HMPAO=六甲基丙烯胺肟)； 两种必须以不同的生物机制起作用的制剂。这些 研究将采用定性和定量SPECT成像技术， 传输计算机断层扫描，在选定的情况下，133-Xe 冲刷技术。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)原发或转移性肿瘤；。(Iv) 特发性癫痫。(5)临床应用与临床疗效比较。 99m-Tc-HMPAO与新型99m-Tc脑显像的疗效比较 放射性药物，特别是那些利用“氧化还原捕捉法”的药物 机制。这些研究将进一步勾勒出定性和 因使用起作用的制剂而产生的数量表现 通过不同的生物机制。(6)CO_2胁迫的评价 加强局部脑血流异常检测的方法 短暂性脑缺血发作患者。这项研究将评估两种药物的临床实用价值 不同放射性药物的技术含量和相对疗效 与这项技术一起使用。

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.