DEVELOPMENT OF 99MTC MYOCARDIAL IMAGING AGENTS

99MTC心肌显像剂的研制

• 批准号: 3336444
• 负责人: RICHARD C ELDER
• 金额: $ 24.95万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336444
• 关键词: Cercopithecidae; Macaca mulatta; X ray crystallography; cats; contrast media; dogs; drug design /synthesis /production; drug metabolism; drug quality /standard; electrochemistry; guinea pigs; heart imaging /visualization /scanning; high performance liquid chromatography; human subject; laboratory rabbit; laboratory rat; ligands; mass spectrometry; myocardial infarction; myocardium disorder; nuclear medicine; radionuclide diagnosis; radiopharmacology; radiotracer; swine; technetium

The primary objective of this research is the development of new, efficacious, myocardial perfusion imaging agents based on the chemistry and nuclear properties of 99m-Tc. This will be accomplished by merging the techniques, equipment and expertise of inorganic chemistry with those of nuclear medicine. Emphasis will be on (1) elucidation of the inorganic chemistry of technetium, utilizing the relatively stable isotope 99-Tc and physical techniques such as single crystal x-ray diffraction and thin-layer spectroelectrochemistry which require only very small quantities of sample, (2) development of synthetic routes to 99m-Tc radiopharmaceuticals that do not involve Sn(II) reduction, (3) development of 99m-Tc myocardial perfusion imaging agents based on well defined, monocationic technetium complexes, (4) elucidation of the chemistry and mechanism of action of those monocationic 99m-Tc myocardial perfusion imaging agents recently developed within this project, e.g. (99m-Tc(dmpe)2Cl2)+ and (99m-Tc(dmpe)3)+ where dmpe = 1,2-bis(dimethylphosphine)ethane, (5) development of in vitro screening procedures to aid in selecting which monocationic 99m-Tc complexes warrant extensive in vivo evaluation, and (6) design and synthesis of new classes of technetium radiopharmaceuticals, the molecular and chemical properties of which can be subtly and systematically modified in order to increase specificity for the myocardium. Animal testing, including the imaging of dogs with induced acute myocardial infarction, will be used to evaluate the efficacy of new radiopharmaceuticals and thereby delineate those molecular and chemical properties than enhance myocardial uptake. The most promising myocardial perfusion imaging agents will be evaluated in human subjects.

本研究的主要目标是开发新的， 有效的心肌灌注显像剂， 99 m-Tc的核特性 这将通过合并 无机化学的技术、设备和专业知识与 核医学 重点将放在（1）无机物的阐明 锝化学，利用相对稳定的同位素99-Tc， 物理技术如单晶X射线衍射和薄层 光谱电化学仅需要非常少量样品， (2)开发99 m-Tc放射性药物的合成路线， 不涉及Sn（II）还原，（3）99 m-Tc心肌的发展 基于定义明确的单阳离子锝的灌注显像剂 配合物，（4）阐明的化学和作用机制， 近年来，单阳离子99 m-Tc心肌灌注显像剂 在本项目中开发的，例如（99 m-Tc（dmpe）2Cl 2）+和 （99 m-Tc（dmpe）3）+，其中dmpe = 1，2-双（二甲基膦）乙烷，（5） 开发体外筛选程序，以帮助选择 单阳离子99 m-Tc配合物保证了广泛的体内评价，和（6） 新型锝放射性药物的设计与合成 其分子和化学性质可以被巧妙而系统地 为了增加对心肌的特异性而修改。 动物 试验，包括对诱发急性心肌梗死的犬进行成像 梗死，将用于评估新的疗效 放射性药物，从而描绘那些分子和化学 比增强心肌摄取的性质。 最有前途的心肌 将在人类受试者中评价灌注成像剂。

项目成果

Myocardial scintigraphy with 99mTc-tris-DMPE in man.

使用 99mTc-tris-DMPE 对人体进行心肌闪烁扫描。

• DOI: 10.1007/bf00295574
• 发表时间: 1984
• 期刊: European journal of nuclear medicine
• 作者: Gerson,MC;Deutsch,EA;Libson,KF;Adolph,RJ;Ketring,AR;Vanderheyden,JL;Williams,CC;Saenger,EL
• 通讯作者: Saenger,EL

Myocardial perfusion imaging with 99mTc-DMPE in man.

使用 99mTc-DMPE 对人体进行心肌灌注成像。

• DOI: 10.1007/bf00253208
• 发表时间: 1983
• 期刊: European journal of nuclear medicine
• 作者: Gerson,MC;Deutsch,EA;Nishiyama,H;Libson,KF;Adolph,RJ;Grossman,LW;Sodd,VJ;Fortman,DL;Vanderheyden,JL;Williams,CC
• 通讯作者: Williams,CC

Comparison of technetium-99m-Q3 and thallium-201 for detection of coronary artery disease in humans.

Technetium-99m-Q3 和铊-201 用于检测人类冠状动脉疾病的比较。

• 发表时间: 1994
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Gerson,MC;Lukes,J;Deutsch,E;Biniakiewicz,D;Washburn,LC;Elgazzar,AH;Elder,RC;Walsh,RA
• 通讯作者: Walsh,RA

Radioactivity standardization of 99mTc and 99Mo.

99mTc 和 99Mo 的放射性标准化。

• DOI: 10.1016/0020-708x(82)90125-9
• 发表时间: 1982
• 期刊: The International journal of applied radiation and isotopes
• 作者: Ayres,RL;Hirshfeld,AT
• 通讯作者: Hirshfeld,AT

The Noah's Ark experiment: species dependent biodistributions of cationic 99mTc complexes.

诺亚方舟实验：阳离子 99mTc 络合物的物种依赖性生物分布。

• DOI: 10.1016/0883-2897(89)90003-2
• 发表时间: 1989
• 期刊: International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
• 作者: Deutsch,E;Ketring,AR;Libson,K;Vanderheyden,JL;Hirth,WW
• 通讯作者: Hirth,WW