NMR RECEPTOR IMAGING

核磁共振受体成像

• 批准号: 6102508
• 负责人: RALPH WEISSLEDER, MD, PHD
• 金额: $ 15.88万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-28 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102508
• 关键词: carbohydrate receptor; cell membrane; chemical conjugate; contrast media; diagnosis design /evaluation; histology; immunoconjugates; iron oxide; laboratory rat; magnetic resonance imaging; membrane structure; neoplasm /cancer diagnosis; neoplastic growth; nuclear magnetic resonance spectroscopy; pancreas neoplasms; pharmacokinetics; receptor

The goal of this research is to extend our previous magnetic resonance (MR) receptor imaging research and develop novel immunospecific contrast agents for the in vivo characterization of cancer. These agents ideally act as ~molecular probes~ for cell surface structures either in normal tissue or in tumor tissue. During the previous funding period, we have successfully synthesized and directed superparamagnetic magnetoconjugates to asialoglycoprotein receptors on hepatocytes and to cholecystokinin (CCK) receptors on pancreas cells and demonstrated improved differentiation of benign and malignant lesions (MR receptor imaging). In the current Project we propose to a) complete the investigations of MR receptor imaging of the pancreas and b) to extend previous research to antigenic and/or receptor sites present on malignant cells. We present data on magnetoimmunoconjugates based on a monocrystalline iron oxide nanocompound (MION) including studies to optimized our coupling strategies and showed that most of the antibody affinity can be retained through conjugation. The proposed research expands on successful in vivo cell culture experiments and in vivo MR imaging with such antibody MION conjugates directed to tumor cell surface structures (MION-L6) or internalized compartments (MION-BR96). We anticipate that results, models and conjugation technology from this research can be used to assess cell surface structure in a variety of neoplastic systems (breast cancer, lung cancer, pelvic malignancies, lymphoma etc.) MR imaging of tumor antigens is expected to allow in vivo typing of malignant tissues, to enhance detection of cancer and to predict efficacy of immunotherapy with chemoconjugates and immunotoxins.

这项研究的目标是扩展我们之前的磁力 磁共振（MR）受体成像研究和开发新型 用于体内表征的免疫特异性造影剂 癌症。 这些试剂理想地充当细胞的〜分子探针〜 正常组织或肿瘤组织的表面结构。 在上一个资助期间，我们成功地 合成并引导超顺磁性磁共轭物 肝细胞上的脱唾液酸糖蛋白受体和胆囊收缩素 (CCK) 受体在胰腺细胞上并被证明得到改善 良恶性病变的鉴别（MR受体 成像）。 在当前项目中，我们建议 a) 完成 胰腺 MR 受体成像的研究和 b) 将先前的研究扩展到存在的抗原和/或受体位点 对恶性细胞。 我们提供的数据 基于单晶氧化铁的磁免疫缀合物 纳米化合物（MION）包括优化我们的研究 偶联策略并表明大多数抗体亲和力 可以通过接合来保留。 拟议的研究 扩展了成功的体内细胞培养实验和体内 使用此类抗体 MION 缀合物进行 MR 成像 肿瘤细胞表面结构（MION-L6）或内化 隔间（MION-BR96）。我们预计结果、模型 本研究的缀合技术可用于 评估各种肿瘤系统中的细胞表面结构 （乳腺癌、肺癌、盆腔恶性肿瘤、淋巴瘤等） 肿瘤抗原的磁共振成像有望实现体内分型 恶性组织，增强癌症检测并预测 化学缀合物免疫疗法的功效和 免疫毒素。