Prediction of the response to antiangiogenic sunitinib therapy by non-invasive hybrid diffuse optics in renal cell carcinoma

通过非侵入性混合漫射光学技术预测肾细胞癌对抗血管生成舒尼替尼治疗的反应

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作者:Miguel Mireles, Gabriela Jiménez-Valerio, Jordi Morales-Dalmau, Johannes D Johansson, Mar Martínez-Lozano, Ernesto E Vidal-Rosas, Valentí Navarro-Pérez, David R Busch, Oriol Casanovas, Turgut Durduran, Clara Vilches

Abstract

In this work, broadband diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) were used to quantify deep tissue hemodynamics in a patient-derived orthotopic xenograft mouse model of clear cell renal cancer undergoing antiangiogenic treatment. A cohort of twenty-two mice were treated with sunitinib and compared to thirteen control untreated mice, and monitored by DRS/DCS. A reduction in total hemoglobin concentration (THC, p = 0.03), oxygen saturation (SO2, p = 0.03) and blood flow index (BFI, p = 0.02) was observed over the treatment course. Early changes in tumor microvascular blood flow and total hemoglobin concentration were correlated with the final microvessel density (p = 0.014) and tumor weight (p = 0.024), respectively. Higher pre-treatment tumor microvascular blood flow was observed in non-responder mice with respect to responder mice, which was statistically predictive of the tumor intrinsic resistance (p = 0.01). This hybrid diffuse optical technique provides a method for predicting tumor intrinsic resistance to antiangiogenic therapy and could be used as predictive biomarker of response to antiangiogenic therapies in pre-clinical models.

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