MIBG ANALOGUE RADIOPHARMACEUTICALS

MIBG 模拟放射性药物

• 批准号: 2733354
• 负责人: GANESAN VAIDYANATHAN
• 金额: $ 21.77万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-08 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733354
• 关键词: analog; antineoplastics; athymic mouse; drug design /synthesis /production; guanidines; halogens; medulloblastoma; neoplasm /cancer pharmacology; neuroblastoma; pharmacokinetics; pheochromocytoma; radionuclides; radiopharmacology; tissue /cell culture

DESCRIPTION (Adapted from Applicant's Abstract): The radiopharmaceutical meta-iodobenzylguanidine (MIBG) has been used in the detection and therapy of neuroendocrine tumors, especially neuroblastoma and pheochromocytoma. Although it is a satisfactory agent for diagnostic applications, the outcome of MIBG therapy is inadequate. The goal of this proposal is to develop an agent which is metabolically more stable, clears faster from normal tissues, and yet is sequestered and retained in tumor. The initial objectives of this proposal are to develop synthetic methods for the preparation of various radioiodinated and [At-211]-labeled MIBG derivatives and to systematically evaluate them in vitro and in vivo. The structural alterations planned include introduction of chlorine, bromine, iodine, nitro and sulfonic acid moieties at the 4-position in the benzene ring of MIBG and replacement of the benzene ring itself with a pyridine ring. Solid-phase synthetic methods will be developed for promising agents. The uptake and retention kinetics in vitro and the effect of several pharmacological agents will be studied using a panel of neuroblastoma, pheochromocytoma and medulloblastoma cell lines. Although not a neuroendocrine tumor, specific uptake of MIBG has been demonstrated in several human medulloblastoma cell lines, and this neoplasm is well suited for [At-211]-therapy. The therapeutic potential of these new [I-131]- and [At-211]-labeled MIBG analogues will be evaluated using thymidine uptake and clonogenic assays in monolayer and spheroid models. Tissue distribution of these agents will be determined in normal mice and athymic mice hosting neuroblastoma, pheochromocytoma, and medulloblastoma xenografts. Strategies to augment tumor-to-normal tissue ratios will be investigated. The outcome of this study should help improve the endoradiotherapy of neuroendocrine tumors and possibly of medulloblastoma.

描述（改编自申请人摘要）：放射性药物