18F FUDR STUDIES IN REGIONAL CHEMOTHERAPY

大约25%的结直肠癌患者 发展肝转移作为疾病复发的初始部位 在尸检中，50%到80%的病例涉及肝脏。 全身化疗反应率一般在15 和25%。 区域注入的反应率 化疗通常在40%到50%之间。 本实验室 已经证明了增加药物输送 增加肿瘤反应。 我们已经开发了一个 通过非药物递送测定肿瘤药物递送的实验方案 侵入性方法 该机构已开发（目前正在雇用） 动态伽玛射线血管造影术研究血流和营养 递送至肝脏和结肠直肠肝转移，使用 氮的短寿命同位素来标记氨基酸。 我们有 开发了18F 5-氟-2 '-脱氧尿苷的实用合成方法 （FUdR），这将允许非侵入性测量肿瘤 通过伽马射线照相术测定药物摄取。 18F 2是回旋加速器 生成的同位素F2;它是一种间接伽马发射体， 半衰期短。 该项目的长期目标是， 通过以下途径施用的FUdR的分布、提取和保留 肝动脉治疗孤立性 不可切除的结直肠肝转移。 使用18 P FUdR， 患者可以通过动态动脉造影进行非侵入性研究， 随着时间 胃十二指肠和肝脏毒性的病因 将被审查。 我们将研究输注速率对肿瘤药物摄取的影响， 全身暴露 可降解淀粉的功效 微球（在模型系统中增加药物摄取），和 血管紧张素II（增加相对肿瘤血流量）将被 考察 由于同位素的半衰期只有两个小时， 涉及少量的辐射，每个患者可能 反复研究，作为自己的对照。

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.