RK-28 is one of the new hypoxic cell radiosensitizers being developed in Japan and has been tested clinically. To reduce its toxicity and increase its sensitizing activity, intratumoral injection of RK-28 was performed during intraoperative radiation therapy for pancreatic cancer. This report presents the results of pharmacokinetic studies performed in 10 of the 17 patients who were administrated intravenous or intratumoral RK-28 during intraoperative radiation therapy. No adverse effects were noted following intravenous or intratumoral injection of the drug. Pharmacokinetic studies demonstrated several metabolites of RK-28 in both serum and tumor tissues. After intratumoral injection, the tumor drug concentration ranged from 123 micrograms/g to 9,292 micrograms/g just after intraoperative radiation therapy (30-50 min after injection of the compound), while the serum concentration ranged from 4.1 to 9.8 micrograms/ml. The tumor drug concentration was 23.3 micrograms/g at 45 min after intravenous injection of RK-28. Thus, intratumoral injection of RK-28 was superior to intravenous administration in this pharmacokinetic study. The combination of intraoperative radiation therapy and intratumoral injection of RK-28 appears to be a feasible treatment method.

中文翻译：

---

新型低氧放射增敏剂RK-28的药代动力学。

RK-28是日本正在开发的新型低氧细胞放射增敏剂之一，并且已经过临床测试。为了降低其毒性并增加其敏化活性，在胰腺癌的术中放射治疗期间进行了肿瘤内注射RK-28。本报告介绍了在术中放疗期间经静脉或瘤内RK-28给药的17例患者中有10例进行了药代动力学研究的结果。静脉内或肿瘤内注射药物后未观察到不良反应。药代动力学研究表明，RK-28在血清和肿瘤组织中都有几种代谢产物。肿瘤内注射后，肿瘤药物浓度范围为123微克/克至9，术中放疗后（注射化合物后30-50分钟）刚好为292微克/克，而血清浓度范围为4.1至9.8微克/毫升。静脉注射RK-28后45分钟，肿瘤药物浓度为23.3微克/克。因此，在该药代动力学研究中，瘤内注射RK-28优于静脉内给药。术中放疗和瘤内注射RK-28的组合似乎是一种可行的治疗方法。