基于高场MRI-光学双模分子成像在头颈部鳞癌边缘微侵润检测的研究

Head and neck squamous cell carcinoma (HNSCC) which had high incidence, greatly threatened human health. Relapse after surgery seriously limited patient prognosis. Head and neck is an area full of nerves and blood vessels. Routine imaging approaches were either unable to detect the infiltrative tumor cells around solid tumor or determine tumor molecular boundary and leaded to inadequate resection. It is critical to establish new approaches to determine actual HNSCC boundary for more effective treatment strategies of HNSCC. Many studies have confirmed that c-Met specially expressed high in HNSCC tumor cells and tumor stem cells. Great correlation was found with c-Met and tumor angiogenesis. We have synthesized small peptide cMBP2 having high binding affinity with c-Met protein. In this project, we will establish a dual modality molecular probe targeting c-Met. We will use MRI to identify precise tumor boundary and optical imaging to recognize tumor infiltration around tumor. Hopefully, the project will apply improve detect actual tumor boundary and guide tumor resection. This project is expected to improve the outcome of HNSCC and patients’ postoperative survival.

头颈部鳞癌（HNSCC）发病率高，严重危害人类健康。术后复发是预后差的重要原因之一。头颈部血管和神经众多，解剖复杂，HNSCC往往呈浸润性生长。研究表明：常规影像检查仅能检出实体瘤大致边界，而无法确定肿瘤真实侵润边界，导致手术残留和放疗失败。因此明确肿瘤边缘微侵润，判断肿瘤的分子边界是提高HNSCC治疗效果的关键环节。前期研究发现，c-Met受体在HNSCC干细胞及肿瘤细胞中明显高表达，且与肿瘤新生血管关系密切，是HNSCC良好的靶标。本项目拟在前期合成c-Met蛋白高效结合的多肽cMBP2基础上，构建一种靶向c-Met受体蛋白的磁共振及光学成像双模态探针，通过高场磁共振和多光谱成像的不同模态成像识别瘤周组织的肿瘤微侵润，进一步明确肿瘤分子边界。本项目的开展有望提高肿瘤边界和微侵润的显示能力，为指导HNSCC手术，提高疗效，减少复发，改善预后，奠定重要的理论和实践基础。

头颈部鳞癌（HNSCC）发病率高，严重危害人类健康。HNSCC往往呈浸润性生长，常规影像仅能检出瘤体大致边界，无法确定真实侵润边界，导致手术残留和放疗失败。因此明确肿瘤边缘微侵润，判断肿瘤的分子边界是提高HNSCC治疗效果的关键环节。前期研究发现，c-Met受体在HNSCC干细胞及肿瘤细胞中明显高表达，且与肿瘤新生血管关系密切，是HNSCC良好的靶标。本项目使用c-Met靶向结合肽(NaGdF4-PEG-cMBP)合成了基于近红外二区(NIR II)荧光成像和T1磁共振成像(MRI)的双模态探针，与目前商业使用的钆相比，该探针具有更强的上转换/NIR II发光及更高的R1弛豫性 (5.871 vs 3.471 mM–1 s–1)。杂合探针的荧光成像显示，该探针可以有效积聚于c-Met靶向的HNSCC肿瘤，并通过双模态T1加权MRI和NIR II荧光成像在皮下和原位HNSCC肿瘤模型中清楚显示。本项目构建了一种靶向c-Met受体蛋白的磁共振及光学成像双模态探针，通过高场磁共振和多光谱成像的不同模态成像识别瘤周组织的肿瘤微侵润，进一步明确肿瘤分子边界，提高肿瘤边界和微侵润的显示能力，为指导HNSCC手术，提高疗效，奠定重要的理论和实践基础。