TY - JOUR

T1 - uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer

T2 - Proof-of-concept in orthotopic xenograft model

AU - Christensen, Anders

AU - Juhl, Karina

AU - Persson, Morten

AU - Charabi, Birgitte Wittenborg

AU - Mortensen, Jann

AU - Kiss, Katalin

AU - Lelkaitis, Giedrius

AU - Rubek, Niclas

AU - von Buchwald, Christian

AU - Kjær, Andreas

PY - 2017/12

Y1 - 2017/12

N2 - Purpose: 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. Experimental design and results: 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 uPARguided robotic cancer surgery was demonstrated. Also, uPAR-PET imaging showed a clear and localized signal in the tongue tumors. Conclusions: This study demonstrated the feasibility of combining two uPARtargeted 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.

AB - Purpose: 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. Experimental design and results: 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 uPARguided robotic cancer surgery was demonstrated. Also, uPAR-PET imaging showed a clear and localized signal in the tongue tumors. Conclusions: This study demonstrated the feasibility of combining two uPARtargeted 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.

KW - Head and neck cancer

KW - Image-guided surgery

KW - PET

KW - Robotic surgery

KW - Tumor margin assessment

KW - uPAR

U2 - 10.18632/oncotarget.14282

DO - 10.18632/oncotarget.14282

M3 - Journal article

C2 - 28039488

AN - SCOPUS:85014074259

VL - 8

SP - 15407

EP - 15419

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 9

ER -