CORE--BIOLOGY

核心--生物学

基本信息

批准号：
6102117
负责人：
URSULA SCHEFFEL
金额：
$ 13.33万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-04-02 至 1999-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6102117
关键词：
autoradiography baboons biomedical facility laboratory mouse laboratory rat ligands microdialysis pharmacokinetics positron emission tomography radionuclides radiopharmacology radiotracer receptor binding technetium tissue /cell culture

项目摘要

The biology core is responsible for in vivo and in vitro characterization and validation of new ligands and radiotracers prepared in this program project, for carrying out pharmacokinetic evaluation of the ligands for organ dosimetry calculations, and for assisting with the preparation of physician-sponsored Investigation of New Drug applications (IND's). Specifically, the biology core tests analogs of known receptor binding compounds using in vitro binding assays for receptor affinity, density, and specificity; performs in vitro receptor autoradiography with promising radioligands to determine their regional distribution; tests the radiolabeled analogs of known receptor ligands for their in vivo distribution and binding to various receptors in the brains of rodents and baboons, and compares them with their radiolabeled parent compounds (when available); validates pharmacologically the tracer as a ligand for a particular binding site; examines the in vivo metabolism of the radiotracers, and determines the whole body biodistribution in rodents to make radiation dose estimates which are necessary for human studies.

生物学核心负责体内和体外表征以及本计划中制备的新配体和放射性示踪剂的验证项目，用于进行配体的药代动力学评价器官剂量测定计算，并协助准备医生发起的新药申请调查 (IND)。具体来说，生物学核心测试已知受体结合的类似物使用体外结合测定法测定化合物的受体亲和力、密度和特异性；进行体外受体放射自显影，具有前景放射性配体以确定其区域分布；测试体内已知受体配体的放射性标记类似物啮齿动物大脑中各种受体的分布和结合狒狒，并将它们与放射性标记的母体化合物进行比较（当可用的）;在药理学上验证示踪剂作为配体特定的结合位点；检查体内代谢放射性示踪剂，并确定啮齿动物的全身生物分布进行人体研究所需的辐射剂量估计。