Chung Yi-Hsiu, Cho I-Chun, Jhang Fujie, Weng Chi-Chang, Lin Gigin, Yu Ching-Fang, Chen Fang-Hsin
Department of Medical Research and Development, Research Division, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333011, Taiwan.
Research Center for Radiation Medicine, Chang Gung University, Taoyuan, 333323, Taiwan.
Radiat Oncol. 2025 Jun 6;20(1):96. doi: 10.1186/s13014-025-02673-0.
Proton beam therapy is an advanced treatment for patients with unresectable hepatocellular carcinoma. However, evaluating the response to treatment with tumor size alone is insufficient. Herein, we used kinetic [18F]-FDG PET and diffusion-weighted MR imaging to monitor the biological responses to proton beam therapy in hepatocellular carcinoma mice to assess treatment efficacy. Murine BNL HCC cells were orthotopically implanted into the livers of 8-week-old male BALB/c mice, which received 20 Gy of the single dose in proton beam therapy. The biological responses to proton beam therapy were assessed on pre-treatment and post-treatment days 1, 3, and 7.
Compared with the not-receiving proton beam therapy group, the treated group led to an increasing trend in tumor K1 values and constant relative SUVs within 7 days on the dynamic PET imaging. On diffusion-weighted MR imaging, the tumor relative apparent diffusion coefficient values significantly increased post-treatment days 3 and 7. Significantly decreased tumor proliferation, cellular density, and cellular uptake of [18F]-FDG on days 1 and/or 3 post-treatment, with a rebound on day 7, were observed in the dynamic profiling of tumor cells ex vivo and in vitro. Vascular remodeling and elevated macrophage infiltrates in the tumor microenvironment were associated with proton beam therapy. However, there were no significant changes in tumor size between the treated and non-treated groups after treatment until day 7.
In vivo kinetic [18F]-FDG PET/MRI techniques can provide a feasible means to assess early liver tumor response to proton beam therapy and predict treatment outcomes.
质子束治疗是不可切除肝细胞癌患者的一种先进治疗方法。然而，仅通过肿瘤大小评估治疗反应是不够的。在此，我们使用动态[18F]-FDG PET和扩散加权磁共振成像来监测肝细胞癌小鼠对质子束治疗的生物学反应，以评估治疗效果。将小鼠BNL HCC细胞原位植入8周龄雄性BALB/c小鼠的肝脏，这些小鼠在质子束治疗中接受单次剂量20 Gy照射。在治疗前以及治疗后第1、3和7天评估对质子束治疗的生物学反应。
与未接受质子束治疗的组相比，治疗组在动态PET成像上7天内肿瘤K1值呈上升趋势，相对SUV值保持恒定。在扩散加权磁共振成像上，治疗后第3天和第7天肿瘤相对表观扩散系数值显著增加。在体外和体内肿瘤细胞的动态分析中，观察到治疗后第1天和/或第3天肿瘤增殖、细胞密度和[18F]-FDG细胞摄取显著降低，第7天出现反弹。肿瘤微环境中的血管重塑和巨噬细胞浸润增加与质子束治疗有关。然而，治疗组和未治疗组在治疗后直到第7天肿瘤大小均无显著变化。
体内动态[18F]-FDG PET/MRI技术可为评估早期肝肿瘤对质子束治疗的反应及预测治疗结果提供一种可行的方法。
