Ultrasound Molecular Imaging of Renal Cell Carcinoma: VEGFR targeted therapy monitored with VEGFR1 and FSHR targeted microbubbles
Ultrasound Molecular Imaging of Renal Cell Carcinoma: VEGFR targeted therapy monitored with VEGFR1 and FSHR targeted microbubbles
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DOI：
10.1038/s41598-020-64433-2
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发表时间：
2020-04-30
影响因子：
4.6
通讯作者：
Lassau, Nathalie
中科院分区：
文献类型：
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作者：
Ingels, Alexandre;Leguerney, Ingrid;Lassau, Nathalie
转移性肾细胞癌的最新治疗进展提供了免疫疗法的组合或与酪氨酸激酶抑制剂（TKI）相关的免疫疗法。目前没有争论选择一种或另一种解决方案。需要使用易于使用的标记物来评估对 TKI 的纵向反应，以确定何时改用免疫疗法。这些新标记物将能够更早地调整治疗策略，以防止肿瘤发展、不必要的毒性和财务成本。本研究评估了超声分子成像在透明细胞肾癌模型 (ccRCC) 中追踪舒尼替尼反应的潜力。我们使用患者来源的异种移植模型进行这项成像研究。携带人类 ccRCC 的小鼠被随机分配接受舒尼替尼治疗与对照组。在第0、7、14和28天用超声分子成像对肿瘤进行成像。对注射非靶向微泡和靶向 VEGFR1 和 FSHR 的微泡后两组之间的信号增强进行量化和比较。舒尼替尼组的肿瘤生长明显减慢。舒尼替尼组在治疗的所有时间（第7、14和28天）VEGFR-1和FSHR分子超声成像信号的表达均显着降低。这些结果证实了研究假设。两组间非靶向微泡超声信号无显着差异。这项研究首次通过基于超声的分子成像证明了 VEGFR1 和 FSHR 追踪 ccRCC 中舒尼替尼纵向反应的潜力。这些结果应该会引发临床应用的发展。
Recent treatment developments for metastatic renal cell carcinoma offer combinations of immunotherapies or immunotherapy associated with tyrosine kinase inhibitors (TKI). There is currently no argument to choose one solution or another. Easy-to-use markers to assess longitudinal responses to TKI are necessary to determine when to switch to immunotherapies. These new markers will enable an earlier adaptation of therapeutic strategy in order to prevent tumor development, unnecessary toxicity and financial costs. This study evaluates the potential of ultrasound molecular imaging to track the response to sunitinib in a clear cell renal carcinoma model (ccRCC). We used a patient-derived xenograft model for this imaging study. Mice harboring human ccRCC were randomized for sunitinib treatment vs. control. The tumors were imaged at days 0, 7, 14 and 28 with ultrasound molecular imaging. Signal enhancement was quantified and compared between the two groups after injections of non-targeted microbubbles and microbubbles targeting VEGFR1 and FSHR. The tumor growth of the sunitinib group was significantly slower. There was a significantly lower expression of both VEGFR-1 and FSHR molecular ultrasound imaging signals in the sunitinib group at all times of treatment (Days 7, 14 and 28). These results confirm the study hypothesis. There was no significant difference between the 2 groups for the non-targeted microbubble ultrasound signal. This study demonstrated for the first time the potential of VEGFR1 and FSHR, by ultrasound-based molecular imaging, to follow-up the longitudinal response to sunitinib in ccRCC. These results should trigger developments for clinical applications.