Abstract
ObjectivesWe have developed a relevant preclinical model associated with a specific imaging protocol dedicated to onco-pharmacology studies in mice.Materials and MethodsWe optimized both the animal model and an ultrasound imaging procedure to follow up longitudinally the lung tumor growth in mice. Moreover we proposed to measure by photoacoustic imaging the intratumoral hypoxia, which is a crucial parameter responsible for resistance to therapies. Finally, we compared ultrasound data to x-ray micro computed tomography and volumetric measurements to validate the relevance of this approach on the NCI-H460 human orthotopic lung tumor.ResultsThis study demonstrates the ability of ultrasound imaging to detect and monitor the in vivo orthotopic lung tumor growth by high resolution ultrasound imaging. This approach enabled us to characterize key biological parameters such as oxygenation, perfusion status and vascularization of tumors.ConclusionSuch an experimental approach has never been reported previously and it would provide a nonradiative tool for assessment of anticancer therapeutic efficacy in mice. Considering the absence of ultrasound propagation through the lung parenchyma, this strategy requires the implantation of tumors strictly located in the superficial posterior part of the lung.
Highlights
Because lung cancer still remains the leading cause of cancer-related death, there is a need to develop more accurate and predictive preclinical protocols and relevant cancer models
This study demonstrates the ability of ultrasound imaging to detect and monitor the in vivo orthotopic lung tumor growth by high resolution ultrasound imaging
Seven days after engraftment the tumor growth was confirmed by Bioluminescence imaging (BLI) (S1D Fig), either in the left or right lung
Summary
Because lung cancer still remains the leading cause of cancer-related death, there is a need to develop more accurate and predictive preclinical protocols and relevant cancer models. Orthotopic lung cancer models have the advantage of being more predictive regarding clinical relevance, including the ability of primary tumors to develop spontaneous metastasis and more predictive regarding the therapeutic response. The implementation and exploration of such orthotopic models allows us to improve our understanding of the biology of cancer to interpret preclinical in vivo results in humans, especially for the potential therapeutic response of anticancer agents. One important parameter in oncology is tumor volume assessment before and during treatments [4]. The pulmonary tumor measurements are predominantly performed with X-ray computed tomography (CT) imaging [5]. For pulmonary preclinical oncology, imaging objectives are to improve the accuracy for determining volumes, without irradiation effects or interferences with the anti-tumor response
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