18F FUDR STUDIES IN REGIONAL CHEMOTHERAPY

大约25%的结直肠癌患者会 将肝转移作为疾病复发的初始部位 而且，在尸检中，50%到80%的病例涉及肝脏。 全身化疗的有效率一般在15%之间 和25%。局部输注卡介苗的有效率 化疗通常在40%到50%之间。我们的实验室 已经证明了药物递送增加之间的相关性 对肿瘤的作用和增强肿瘤的反应。我们已经开发出一种 确定非肿瘤药物给药的实验方案 侵入性的方法。 这家机构已经开发(并正在招聘) 动态伽马核素扫描研究血流和营养 向肝脏和结直肠癌肝转移的递送，使用 氮的短暂的同位素，用来标记氨基酸。我们有 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 通过伽马闪烁照相进行药物摄取。18F2是一台回旋加速器- 生成的F2的同位素；它是一种间接的伽马发射器，具有 半衰期很短。 该项目的长期目标是将 氟尿嘧啶经皮给药的分布、提取和保留 肝动脉治疗孤立性肝动脉 不能切除的结直肠癌肝转移。使用18P FUDR， 动态核素显像可对患者进行无创性研究 随着时间的推移。胃十二指肠和肝毒性的病因学研究 将会被检查。 我们将研究输液速度对肿瘤药物摄取的影响和 全身性暴露。可降解淀粉的功效 微球(在模型系统中增加药物摄取)，以及 血管紧张素II(增加相对肿瘤血流量)将 检查过了。由于同位素的半衰期只有两个小时，而且只有 涉及少量辐射，每个患者都可能 反复学习，充当自己的控制者。

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.