Background: Magnetic resonance imaging (MRI) is a non-invasive imaging modality which, in conjunction with biopsies, provide a qualitative assessment of tumor response to treatment. Intravenous injection of contrast agents such as fluorine (19F) nanoemulsions labels systemic macrophages, which can, then, be tracked in real time with MRI. This method can provide quantifiable insights into the behavior of tumor-associated macrophages (TAMs) in the tumor microenvironment and macrophage recruitment during therapy. Methods: Female mice received mammary fat pad injections of murine breast or colon cancer cell lines. The mice then received an intravenous19F nanoemulsion injection, followed by a baseline19F MRI. For each cancer model, half of the mice then received 8 Gy of localized radiation therapy (RT), while others remained untreated. The mice were monitored for two weeks for tumor growth and9F signal using MRI. Results: Across both cohorts, the RT-treated groups presented significant tumor growth reduction or arrest, contrary to the untreated groups. Similarly, the fluorine signal in treated groups increased significantly as early as four days post therapy. The fluorine signal change correlated to tumor volumes irrespective of time. Conclusion: These results demonstrate the potential of19F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regard to tumor growth.
背景:磁共振成像(MRI)是一种无创成像技术,结合活检可对肿瘤治疗反应进行定性评估。静脉注射氟(19F)纳米乳剂等造影剂可标记全身巨噬细胞,随后通过MRI实时追踪。该方法能够量化分析肿瘤微环境中肿瘤相关巨噬细胞(TAMs)的行为特征及治疗过程中的巨噬细胞募集动态。方法:对雌性小鼠乳腺脂肪垫注射鼠源乳腺癌或结肠癌细胞系,随后静脉注射19F纳米乳剂并进行基线19F MRI扫描。针对每种癌症模型,半数小鼠接受8 Gy局部放射治疗(RT),其余作为未治疗对照组。通过MRI连续两周监测小鼠肿瘤生长情况及19F信号变化。结果:在所有实验组中,接受RT治疗的小鼠均呈现显著的肿瘤生长抑制或停滞,与未治疗组形成鲜明对比。同时,治疗组氟信号早在治疗后第四天即显著增强。无论时间因素如何,氟信号变化始终与肿瘤体积呈相关性。结论:本研究证实19F MRI在放射治疗期间无创追踪巨噬细胞的可行性,并揭示其对肿瘤生长预测的潜在预后价值。
Magnetic Resonance Imaging of Macrophage Response to Radiation Therapy