Yttrium-90 (90Y)-polymer composite (RadioGel™) is a new cancer therapeutic agent for treating solid tumors by direct interstitial injection. The 90Y-composite comprises insoluble, microscopic yttrium-phosphate particles carried by a sterile, injectable water-polymer (hydrogel) solution that can be placed directly by needle injection into solid tumors. The yttrium-90-RadioGel™ agent was designed to provide a safe, effective, localized, high-dose beta radiation for treating solid tumors. The properties of 90Y-RadioGel™ also make it a relatively safe agent for health care personnel who prepare, handle, and administer the material. The purpose of this work was to demonstrate and characterize radiation safety of the injectable 90Y-RadioGel™ therapeutic agent. Safety in the patient is defined by its ability to target precisely and remain confined within tumor tissue so that radiation doses are imparted to the tumor and not to normal organs and tissues. Radiation safety for health care personnel is defined by the low radiation doses received by persons who prepare and administer the agent. These safety features were demonstrated during experiments, first involving laboratory rabbits and second in cat and dog animal patients that were treated clinically for sarcoma tumors. This paper focuses mainly on the rabbit tissue biodistribution study; follow-on clinical application in cat and dog subjects confirmed the rabbit results. Implanted VX2 liver tumors in the hind limbs of 26 New Zealand White rabbits were treated using tracer amounts of either (a) 90Y-RadioGel™ or (b) 90Y-microparticles in phosphate-buffered saline (PBS) without the gel carrier. Tumor and margin injections were interstitial. Rabbits were euthanized at 48 h or 10 d following injection. Blood and tissues (tumor or tumor margins, liver, lymph nodes, rib bone, kidney, spleen) were collected for liquid scintillation counting using wet-ash procedures. Biodistribution was also analyzed at 10 d post-injection using micro-computed tomography. Thirteen cat and dog subjects were also treated clinically for sarcomas. Liquid scintillation counting at 48 h post-injection of tumors or margins with 90Y-RadioGel™ showed that significant radioactivity was measurable only at the site of administration and that radioactivity above detector background was not found in blood or peripheral organs and tissues. At 10 d post-injection, microCT showed that yttrium phosphate microparticles were confined to the injection site. Yttrium-90 remained where placed and did not migrate away in significant amounts from the injection site. Radiation doses were confined mainly to tumors and margin tissues. During preparation and administration, radiation doses to hands and body of study personnel were negligible. This work showed that 90Y-RadioGel™ can be safely prepared and administered and that radiation doses to cancer patients are confined to tumor and margin tissues rather than to critical normal organs and tissues.

中文翻译：

---

钇 90 聚合物复合材料 (RadioGel™) 在实体瘤治疗中的辐射安全性。

Yttrium-90 (90Y)-聚合物复合材料（RadioGel™）是一种通过直接组织间注射治疗实体瘤的新型癌症治疗剂。90Y-复合材料包含不溶性的微观磷酸钇颗粒，其由无菌可注射水聚合物（水凝胶）溶液携带，可以通过针头注射直接放入实体瘤中。yttrium-90-RadioGel™ 试剂旨在为治疗实体瘤提供安全、有效、局部、高剂量的 β 辐射。90Y-RadioGel™ 的特性也使其成为准备、处理和管理该材料的医疗保健人员相对安全的制剂。这项工作的目的是证明和表征可注射 90Y-RadioGel™ 治疗剂的辐射安全性。患者的安全性取决于其精确瞄准并保持限制在肿瘤组织内的能力，从而使辐射剂量传递到肿瘤而不是正常器官和组织。卫生保健人员的辐射安全是指制备和施用药剂的人员所接受的低辐射剂量。这些安全特性在实验中得到了证明，首先涉及实验室兔子，其次涉及接受临床肉瘤肿瘤治疗的猫和狗动物患者。本文主要针对兔组织生物分布研究；猫和狗受试者的后续临床应用证实了兔子的结果。使用示踪剂量的 (a) 90Y-RadioGel™ 或 (b) 不含凝胶载体的磷酸盐缓冲盐水 (PBS) 中的 90Y-微粒治疗 26 只新西兰白兔后肢植入的 VX2 肝肿瘤。肿瘤和边缘注射是间质的。注射后48小时或10天对兔子实施安乐死。收集血液和组织（肿瘤或肿瘤边缘、肝脏、淋巴结、肋骨、肾脏、脾脏），使用湿灰程序进行液体闪烁计数。还使用微型计算机断层扫描在注射后 10 天分析生物分布。十三名猫和狗受试者也接受了肉瘤的临床治疗。使用 90Y-RadioGel™ 注射肿瘤或边缘 48 小时后进行的液体闪烁计数表明，仅在给药部位可测量到显着的放射性，并且在血液或外周器官和组织中未发现高于检测器背景的放射性。注射后 10 天，microCT 显示磷酸钇微粒被限制在注射部位。钇 90 保留在放置的位置，并且没有大量从注射部位迁移走。放射剂量主要局限于肿瘤和边缘组织。在制备和给药过程中，研究人员手部和身体受到的辐射剂量可以忽略不计。这项工作表明，90Y-RadioGel™ 可以安全地制备和施用，并且癌症患者的辐射剂量仅限于肿瘤和边缘组织，而不是关键的正常器官和组织。