Department of Gastroenterological Surgery, Oslo University Hospital, The Radium Hospital, Oslo, Norway.
Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231192902. doi: 10.1177/15330338231192902.
Despite extensive treatment with surgery and chemotherapy many patients with peritoneal metastases from colorectal cancer experience intraperitoneal disease relapse. The α-emitting radium-labelled microparticle radionuclide therapeutic Radspherin® is being explored as a novel treatment option for these patients. Radspherin® is specially designed to give local radiation to the surface of the peritoneal cavity and potentially kill remaining attached micrometastases as well as free-floating cancer cells, thus preventing future relapse. The effect of Radspherin® on the immune system is not known. Systemic and local inflammatory responses were analyzed in plasma, intraperitoneal fluid and urine collected prospectively as part of a phase 1 dose-escalation study of intraperitoneal instillation of the α-emitting therapeutic radiopharmaceutical Radspherin®, at baseline and the first 7 postoperative days from nine patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. All patients additionally received intraperitoneal instillation of Radspherin® on postoperative day 2. Complement activation products C3bc and the terminal complement complex were analyzed using enzyme-linked immunosorbent assay. Cytokines ( = 27), including interleukins, chemokines, interferons and growth factors, were analyzed using multiplex technique. The time course and magnitude of the postoperative cytokine response after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy displayed a modest systemic response in plasma, in contrast to a substantial local intraperitoneal response. After administration of Radspherin®, a significant increase ( < 0.05) in TNF and MIP-1β was observed in both plasma and peritoneal fluid, whereas IL-9 increased only in plasma and IFNγ and IL1-RA only in peritoneal fluid. Only minor changes were seen for the majority of the inflammatory markers after Radspherin® administration. Our study showed a predominately local rather than systemic inflammatory response to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Radspherin® had overall modest impact on the inflammation.
尽管进行了广泛的手术和化疗治疗，但许多结直肠癌腹膜转移患者仍会出现腹膜内疾病复发。α 发射镭标记的微粒放射性核素治疗药物 Radspherin® 正被探索作为这些患者的一种新的治疗选择。Radspherin® 专门设计用于对腹腔表面进行局部放射治疗，并可能杀死残留的附着微转移灶和游离癌细胞，从而防止未来复发。Radspherin® 对免疫系统的影响尚不清楚。作为一项针对α发射治疗性放射性药物 Radspherin® 腹腔内滴注的 1 期剂量递增研究的一部分，前瞻性地分析了 9 例接受细胞减灭术和腹腔内热化疗的患者在基线和术后第 7 天收集的血浆、腹腔液和尿液中的全身和局部炎症反应。所有患者在术后第 2 天还接受了腹腔内滴注 Radspherin®。使用酶联免疫吸附试验分析补体激活产物 C3bc 和末端补体复合物。使用多重技术分析细胞因子（ = 27），包括白细胞介素、趋化因子、干扰素和生长因子。细胞减灭术和腹腔内热化疗后的术后细胞因子反应的时间过程和幅度显示出血浆中适度的全身反应，而腹腔内则表现出显著的局部反应。给予 Radspherin®后，在血浆和腹腔液中均观察到 TNF 和 MIP-1β 的显著增加（ < 0.05），而 IL-9 仅在血浆中增加，IFNγ 和 IL1-RA 仅在腹腔液中增加。给予 Radspherin®后，大多数炎症标志物的变化较小。我们的研究显示，细胞减灭术和腹腔内热化疗主要引起局部而非全身炎症反应。Radspherin®对炎症的总体影响较小。
