18F FUDR STUDIES IN REGIONAL CHEMOTHERAPY

18F 局部化疗中的 FUDR 研究

• 批准号: 3079852
• 负责人: Elin R Sigurdson
• 金额: $ 6.26万
• 依托单位: MEMORIAL HOSPITAL FOR CANCER & ALLIED DI
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3079852
• 关键词: 5 fluorouridine; aminoacid; angiotensin II; antineoplastics; diet route /schedule; drug adverse effect; drug delivery systems; drug metabolism; human subject; human therapy evaluation; intraarterial administration; liver metabolism; liver neoplasms; metastasis; neoplasm /cancer blood supply; neoplasm /cancer chemotherapy; neoplasm /cancer radionuclide therapy; noninvasive diagnosis; radionuclide imaging /scanning; radiotracer; vasoactive agent

Approximately 25% of patients with colorectal cancer will develop liver metastases as their initial site of disease recurrence and, at autopsy, the liver is involved in 50 to 80% of cases. Systemic chemotherapy response rates are generally between 15 and 25%. The response rates from regional infusion of chemotherapy are usually between 40 and 50%. Our laboratory has demonstrated a correlation between increased drug delivery to tumor and increased tumor response. We have developed an experimental protocol to determine tumor drug delivery by non- invasive methods. This institution has developed (and is currently employing) dynamic gamma scintigraphy to study blood flow and nutrient delivery to the liver and to colorectal hepatic metastases, using the short-lived isotope of nitrogen to label amino acids. We have developed a practical synthesis of 18F 5-fluoro-2'-deoxyuridine (FUdR), which will permit non-invasive measurements of tumor drug uptake by gamma scintigraphy. 18F2 is a cyclotron- generated isotope of F2; it is an indirect gamma emitter with a short half-life. The long-term objectives of this project are to characterized the distribution, extraction and retention of FUdR administered via the hepatic artery for treatment of patients with isolated unresectable colorectal hepatic metastases. Using 18P FUdR, patients can be studied non-invasively by dynamic scintigraphy over time. The etiology of gastroduodenal and hepatic toxicity will be examined. We will study the effect of infusion rate on tumor drug uptake and on systemic exposure. The efficacy of degradable starch microspheres (which increase drug uptake in model systems), and angiotensin II (which increases relative tumor blood flow) will be examined. Since the isotope half-life is only two hours, and only small amounts of radiation are involved, each patient may undergo repeated studies, acting as his own control.

大约 25% 的结直肠癌患者会 发展为肝转移作为疾病复发的初始部位 尸检显示，50% 至 80% 的病例累及肝脏。 全身化疗反应率一般在 15 和25%。 区域输注的反应率 化疗通常在 40% 至 50% 之间。 我们的实验室 已证明药物输送增加之间存在相关性 抗肿瘤并增加肿瘤反应。 我们开发了一个 确定非肿瘤药物输送的实验方案 侵入性方法。 该机构已经开发（并且目前正在雇用） 动态伽马闪烁扫描研究血流和营养 递送至肝脏和结直肠肝转移，使用 用于标记氨基酸的氮的短寿命同位素。 我们有 开发了 18F 5-氟-2'-脱氧尿苷的实用合成 （FUdR），这将允许对肿瘤进行非侵入性测量 通过伽马闪烁扫描进行药物摄取。 18F2是一个回旋加速器 生成F2同位素；它是一个间接伽马发射器 半衰期短。 该项目的长期目标是表征 FUdR 的分布、提取和保留 肝动脉治疗孤立性肝病患者 不可切除的结直肠肝转移。 使用 18P FUdR， 可以通过动态闪烁扫描对患者进行非侵入性研究 随着时间的推移。 胃十二指肠和肝毒性的病因学 将接受检查。 我们将研究输注速率对肿瘤药物摄取的影响以及 关于全身暴露。 可降解淀粉的功效 微球（增加模型系统中的药物摄取），以及 血管紧张素 II（增加相对肿瘤血流量）将 检查了。 由于同位素的半衰期只有两个小时，而且 涉及少量辐射，每个患者可能 进行反复研究，充当自己的对照。