P-31 MRS: CHEMOTHERAPY RESPONSE PREDICTOR

P-31 MRS：化疗反应预测器

• 批准号: 3186431
• 负责人: JEFFREY L EVELHOCH
• 金额: $ 13.28万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3186431
• 关键词: alkylating agents; antimetabolites; antineoplastics; cis platinum compound; combination cancer therapy; combination chemotherapy; cytosine arabinoside; disease /disorder model; dosage; doxorubicin; drug metabolism; drug resistance; flavones; laboratory mouse; neoplasm /cancer chemotherapy; neoplasm /cancer radionuclide therapy; neoplastic cell culture for noncancer research; neoplastic growth; nuclear magnetic resonance spectroscopy

The main objective of this application is to evaluate critically the potential for in vivo 31P MRS to provide predictive markers of tumor response to chemotherapy before and/or early after treatment with a "test" dose (i.e., a fraction of the maximum tolerated dosage). Because MRS is nondestructive, the methodology developed and evaluated in these studies, using well-defined murine tumor models, can be applied in the clinic. Availability of a clinical predictor of chemotherapeutic response would allow selection of a more effective, individualized therapy. A special emphasis is place on identifying markers which are both specific to a therapeutic response in tumors and sensitive to clinically- relevant "test" doses. Response-specific markers for chemotherapeutic agents from three major classes (i.e., DNA-binder-intercalators, alkylating agents and antimetabolites) and a new antitumor agent of unknown mechanism will be identified by using sets of tumors that contain one tumor clearly sensitive to each agent as well as counterparts with either innate or induced resistance to that agent. To determine which, if any, 31P MRS metabolic characteristics of tumors present prior to initial treatment are predictive markers of response to chemotherapy, those characteristics present in the sensitive and resistant tumors will be compared. To determine which, if any, changes in the 31P MRS metabolic characteristics in response to a "test" dose of chemotherapeutic agent provide predictive markers of response, the changes in those characteristics observed in the sensitive and resistant tumors will be compared. To determine the earliest time after treatment any change are evident in the 31P MRS metabolic characteristics data will be acquired prior to and 1h, 5.5h, 10h, 24h, and ever 24h thereafter until the tumor mass either is reduced by 50% or regrows. To both examine the dose- response relationship of such changes and determine the minimum dose required to elicit those changes, animals treated with doses of either 80% maximum tolerated dosage (MTD), 50% MTD or 25% MTD will be observed by 31P MRS prior to and from the earliest time after treatment such changes were noted until the tumor mass either is reduced by 50% or regrows.

该应用的主要目的是批判性评估 体内31p MRS的潜力提供肿瘤的预测标记 对化学疗法的反应和/或用A “测试”剂量（即最大耐受剂量的一部分）。 因为 MRS是无损的，在这些方法中开发和评估的方法 使用明确定义的鼠肿瘤模型的研究可以应用于 诊所。 化学治疗的临床预测指标的可用性 响应将允许选择更有效，个性化的 治疗。 特别重点是识别既有的标记 特定于肿瘤的治疗反应，对临床敏感 相关的“测试”剂量。 化学治疗的反应特异性标记 来自三个主要类别的代理商（即DNA-绑定器， 烷基化剂和抗代谢物）和一种新的抗肿瘤剂 未知机制将通过使用包含的肿瘤集来识别 一个肿瘤显然对每个药物以及与 对该试剂的先天或诱导的抗性。确定哪个，是否 任何，在初始之前存在的肿瘤的31p MRS代谢特征 治疗是对化学疗法反应的预测标志物，这些标志 敏感和抗性肿瘤中存在的特征将是 比较的。 确定31p MRS代谢中的哪种（如果有）发生变化 响应“测试”化学治疗剂的特征 提供响应的预测标记，这些变化 在敏感和抗性肿瘤中观察到的特征将是 比较的。 为了确定治疗后的最早时间，任何变化是 将获取31p MRS代谢特征数据中的明显数据 之前和1小时，5.5h，10h，24h，此后24H，直到肿瘤 质量要么降低50％或再生。 两者都检查剂量 - 这种变化的响应关系并确定最小剂量 需要引起这些变化，用剂量治疗的动物 将观察到80％最大耐受剂量（MTD），50％MTD或25％MTD 到31p MRS之前和从治疗后的最早时间开始 直到肿瘤质量降低50％或 再生。