Young D, Vine E, Ghanbarpour A, Shani J, Siemsen J K, Wolf W
Nuklearmedizin. 1982 Feb;21(1):1-7.
5-Fluorouracil (5-FU) is an effective anti-tumor drug, which has been used both as a single agent and in combination with other chemotherapeutic agents for the treatment of tumors such as breast and colorectal carcinoma. We synthesized 5-FU with trace amounts of 18F-5-FU and administered the compounds intravenously to 6 cancer patients. The patients were scanned at 2 hr intervals for 12 hrs and their urine collected whenever possible. We also injected 5-FU with the tracer 18F-5-FU, at pharmacological doses, into non-tumored rats, and sampled their bile and blood for 95 mins post-injection. For comparison, 2-14C-5-FU was injected into non-tumored rats and their bile and blood sampled at the same intervals. Minute quantities of rat bile and serum were analyzed chromatographically by high-performance TLC. 5-FU and two of its metabolites (FBAL and FUPA) were identified and quantified by this technique. Both percentage and absolute amounts of 5-FU in the bile follow comparative kinetic patterns. While the liver and the urinary bladder were clearly observable in all 16 patients, the detectability of the gall-bladder was correlated to the inverse of the alkaline phosphatase level in the blood. This work suggests that the diversity of the 5-FU metabolism in cancer patients may allow the use of 18F-5-FU as a probe for understanding those individual variabilities in clinical situations.
5-氟尿嘧啶（5-FU）是一种有效的抗肿瘤药物，已被用作单一药物以及与其他化疗药物联合用于治疗乳腺癌和结直肠癌等肿瘤。我们合成了含有微量18F-5-FU的5-FU，并将这些化合物静脉注射给6名癌症患者。患者每隔2小时扫描一次，共扫描12小时，并尽可能收集尿液。我们还将药理剂量的5-FU与示踪剂18F-5-FU注射到未患肿瘤的大鼠体内，并在注射后95分钟采集它们的胆汁和血液样本。作为对照，将2-14C-5-FU注射到未患肿瘤的大鼠体内，并在相同时间间隔采集它们的胆汁和血液样本。用高效薄层层析法对微量大鼠胆汁和血清进行色谱分析。用该技术鉴定并定量了5-FU及其两种代谢产物（FBAL和FUPA）。胆汁中5-FU的百分比和绝对量均呈现出比较性的动力学模式。在所有16名患者中，肝脏和膀胱都清晰可见，而胆囊的可检测性与血液中碱性磷酸酶水平呈负相关。这项研究表明，癌症患者中5-FU代谢的多样性可能使18F-5-FU能够用作一种探针，以了解临床情况下的个体差异。
