In Vivo Three-dimensional Visualizing Tumor Hypoxia In Orthotopic Nasopharyngeal Carcinoma With FMT-CT/ MSOT

Nasopharyngeal carcinoma(NPC)is a common malignant disease in south China,especially in Guangdong Province.Radiotherapy is the mainstay of treatment for NPCs.Recently radiotherapy along with chemotherapy have dramatically improved survival rates,however,tumor relapse and distant metastasis after radiotherapy as radiation resistance remains a serious obstacle to successful treatment in NPCs.Tumor hypoxia was reported to play a critical role in radiotherapy resistance.Locally increasing the radiation dose in hypoxic area is crucial to improve the curative effect of advanced NPCs,especially when recently developed intensity-modulated radiotherapy makes finely regulating dose distribution possible.Thus,the accurate threedimensional positioning of hypoxia is especially vital for radiotherapy of NPCs.However,its clinical approach relies heavily on the needle biopsy currently,and noninvasive imaging strategies for hypoxia remains extremely underexplored.Here,we proposed a multi-modality imaging method,which combined the hybrid fluorescence molecular tomography-computed tomography(FMT-CT)and the multispectral optoacoustic tomography(MSOT).A CAIX-specific molecular probe was developed and successfully applied to targeting tumor hypoxia both in early and advance stage of NPCs.The specific research content as follows.1)A CAIX-specific molecular probe named CAIX-800 was synthesized to test the purity and basic optical properties,and to verify its targeting efficiency and specificity both in vitro and in vivo.2)The models of early NPCs and lymph node metastasis at advanced stage were further established.Based on a hypoxia-targeted probe mentioned above,a novel hypoxic multimodal imaging strategy is proposed.At the earlier stage of NPCs,the highly sensitive FMT-CT enabled a precise 3D localization of the hypoxic tumor with high contrast.At the advanced stage,MSOT offered an intuitively 3D visualization of primary tumors and nodal metastases,and provided a multispectral analysis of the biomarker and hemoglobin with high resolution.The combination of high sensitivity and high resolution from FMT-CT and MSOT could not only detect the hypoxic tumors in small size,but also visualize the primary and nodal metastases of hypoxia in 3D.The novel imaging strategy may potentially benefit individualized therapy of NPCs in the future,with broad application prospect in clinic.