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头颈部癌症的多模态影像引导手术和光动力介入治疗:从原发肿瘤到转移引流。

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage.

机构信息

Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Canada.

Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Canada. Medical Isotopes Research Center, Peking University, Beijing, China.

出版信息

Clin Cancer Res. 2016 Feb 15;22(4):961-70. doi: 10.1158/1078-0432.CCR-15-1235. Epub 2015 Oct 13.

Abstract

PURPOSE

The low survival rate of head and neck cancer (HNC) patients is attributable to late disease diagnosis and high recurrence rate. Current HNC staging has inadequate accuracy and low sensitivity for effective diagnosis and treatment management. The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP), intrinsically capable of positron emission tomography (PET), fluorescence imaging, and photodynamic therapy (PDT), shows great potential to enhance the accuracy of HNC staging and potentially HNC management.

EXPERIMENTAL DESIGN

Using a clinically relevant VX-2 buccal carcinoma rabbit model that is able to consistently develop metastasis to regional lymph nodes after tumor induction, we investigated the abilities of PLP for HNC diagnosis and management.

RESULTS

PLPs facilitated accurate detection of primary tumor and metastatic nodes (their PET image signal to surrounding muscle ratios were 10.0 and 7.3, respectively), and provided visualization of the lymphatic drainage from tumor to regional lymph nodes by both preoperative PET and intraoperative fluorescence imaging, allowing the identification of unknown primaries and recurrent tumors. PLP-PDT significantly enhanced cell apoptosis in mouse tumors (73.2% of PLP-PDT group vs 7.1% of PLP alone group) and demonstrated complete eradication of primary tumors and obstruction of tumor metastasis in HNC rabbit model without toxicity in normal tissues or damage to adjacent critical structures.

CONCLUSIONS

PLPs provide a multimodal imaging and therapy platform that could enhance HNC diagnosis by integrating PET/computed tomography and fluorescence imaging, and improve HNC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgery and PDT.

摘要

目的

头颈部癌症(HNC)患者的生存率低,原因是疾病诊断较晚且复发率高。目前的 HNC 分期对于有效诊断和治疗管理的准确性和灵敏度都不够高。多模态卟啉脂蛋白模拟纳米颗粒(PLP)具有内在的正电子发射断层扫描(PET)、荧光成像和光动力疗法(PDT)能力,有望提高 HNC 分期的准确性,并有可能改善 HNC 的管理。

实验设计

我们使用了一种临床相关的 VX-2 颊癌兔模型,该模型在肿瘤诱导后能够持续向区域淋巴结转移,研究了 PLP 对头颈部癌症诊断和管理的能力。

结果

PLP 促进了对原发性肿瘤和转移性淋巴结的准确检测(其 PET 图像信号与周围肌肉的比值分别为 10.0 和 7.3),并通过术前 PET 和术中荧光成像提供了肿瘤向区域淋巴结的淋巴引流可视化,从而能够识别未知原发性肿瘤和复发性肿瘤。PLP-PDT 显著增强了小鼠肿瘤中的细胞凋亡(PLP-PDT 组为 73.2%,而 PLP 组为 7.1%),并在 HNC 兔模型中完全消除了原发性肿瘤,阻止了肿瘤转移,同时在正常组织中没有毒性,也没有对邻近的关键结构造成损害。

结论

PLP 提供了一种多模态成像和治疗平台,通过整合 PET/计算机断层扫描和荧光成像,可以提高 HNC 的诊断准确性,并通过荧光引导手术和 PDT 来定制治疗,从而提高 HNC 的治疗效果和特异性。

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