uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer: proof-of-concept in orthotopic xenograft model.
uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer: proof-of-concept in orthotopic xenograft model.
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DOI：
10.18632/oncotarget.14282
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发表时间：
2017-02-28
期刊：
影响因子：
--
通讯作者：
Kjær A
中科院分区：
文献类型：
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作者：
Christensen A;Juhl K;Persson M;Charabi BW;Mortensen J;Kiss K;Lelkaitis G;Rubek N;von Buchwald C;Kjær A
尿激酶样纤溶酶原激活剂受体 (uPAR) 在多种癌症类型中过度表达，因此是一个有吸引力的成像靶点。本研究的目的是评估两种 uPAR 靶向探针在人类异种移植舌癌模型中进行 PET 和荧光肿瘤成像的可行性。通过生物发光成像（BLI）和 MRI 监测舌癌的肿瘤生长。全身注射ICG-Glu-Glu-AE105（荧光剂）或64Cu-DOTA-AE105（PET剂），进行荧光成像或PET/CT成像。收集组织用于微荧光成像和组织学。在原发肿瘤中检测到清晰的荧光信号，平均体内肿瘤与背景比为 2.5。实时荧光引导肿瘤切除是可能的，并且可以定位亚毫米肿瘤沉积物。组织学分析显示荧光信号、uPAR 表达和肿瘤沉积物的共定位。此外，uPAR引导的机器人癌症手术的可行性也得到了证明。此外，uPAR-PET 成像在舌肿瘤中显示出清晰的局部信号。这项研究证明了在临床前头颈癌模型中结合两种 uPAR 靶向探针的可行性。 PET 模式提供术前非侵入性肿瘤成像，光学模式允许实时荧光引导肿瘤检测和切除。该平台的临床转化似乎很有希望。
Urokinase-like Plasminogen Activator Receptor (uPAR) is overexpressed in a variety of carcinoma types, and therefore represents an attractive imaging target. The aim of this study was to assess the feasibility of two uPAR-targeted probes for PET and fluorescence tumor imaging in a human xenograft tongue cancer model. Tumor growth of tongue cancer was monitored by bioluminescence imaging (BLI) and MRI. Either ICG-Glu-Glu-AE105 (fluorescent agent) or 64Cu-DOTA-AE105 (PET agent) was injected systemically, and fluorescence imaging or PET/CT imaging was performed. Tissue was collected for micro-fluorescence imaging and histology. A clear fluorescent signal was detected in the primary tumor with a mean in vivo tumor-to-background ratio of 2.5. Real-time fluorescence-guided tumor resection was possible, and sub-millimeter tumor deposits could be localized. Histological analysis showed co-localization of the fluorescent signal, uPAR expression and tumor deposits. In addition, the feasibility of uPAR-guided robotic cancer surgery was demonstrated. Also, uPAR-PET imaging showed a clear and localized signal in the tongue tumors. This study demonstrated the feasibility of combining two uPAR-targeted probes in a preclinical head and neck cancer model. The PET modality provided preoperative non-invasive tumor imaging and the optical modality allowed for real-time fluorescence-guided tumor detection and resection. Clinical translation of this platform seems promising.