Improved surgical resection of metastatic pancreatic cancer using uPAR targeted in vivo fluorescent guidance: comparison with traditional white light surgery
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Improved surgical resection of metastatic pancreatic cancer using uPAR targeted in vivo fluorescent guidance : comparison with traditional white light surgery. / Juhl, Karina; Christensen, Anders; Rubek, Niclas; Karnov, Kirstine Kim Schmidt; von Buchwald, Christian; Kjaer, Andreas.
I: OncoTarget, Bind 10, Nr. 59, 10.2019, s. 6308-6316.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Improved surgical resection of metastatic pancreatic cancer using uPAR targeted in vivo fluorescent guidance
T2 - comparison with traditional white light surgery
AU - Juhl, Karina
AU - Christensen, Anders
AU - Rubek, Niclas
AU - Karnov, Kirstine Kim Schmidt
AU - von Buchwald, Christian
AU - Kjaer, Andreas
N1 - Copyright: © 2019 Juhl et al.
PY - 2019/10
Y1 - 2019/10
N2 - Pancreatic cancer remains one of the deadliest cancers. The five-year survival rates have been reported as 3%. Radical surgical tumor resection is critical for improved outcome and the low survival rate for pancreatic cancer is due to lack of other effective treatments and here optical guided surgery could be a solution for better surgical outcome. In the present study, we targeted the urokinase plasminogen activator receptor (uPAR) with a peptide conjugated with the fluophore ICG (ICG-Glu-Glu-AE105) for optical imaging. In the first part of the study we aimed to validate ICG-Glu-Glu-AE105 for resection of the primary tumor and metastases in an orthotopic human xenograft pancreatic cancer model. In the second part of the study we aimed to investigate if fluorescent-guided imaging could locate additional metastases following conventional removal of metastasis under normal white light surgery. Our study showed that ICG-Glu-Glu-AE105 was an excellent probe for intraoperative optical imaging with a mean tumor-to-background ratio (TBR) for the primary tumor of 3.5 and a TBR for the metastases of 3.4. Further, a benefit using intraoperative fluorescent guidance yielded identification of an additional 14% metastases compared to using normal white light surgery. In 4 of 8 mice there were identified additional metastases with uPAR optical imaging compared to white light. In conclusion, the uPAR-targeted optical probe ICG-Glu-Glu-AE105 enables intraoperative optical cancer imaging, including robotic surgery, and may be a benefit during intended radical resection of disseminated pancreas cancer by finding more metastasis than with traditional white light surgery.
AB - Pancreatic cancer remains one of the deadliest cancers. The five-year survival rates have been reported as 3%. Radical surgical tumor resection is critical for improved outcome and the low survival rate for pancreatic cancer is due to lack of other effective treatments and here optical guided surgery could be a solution for better surgical outcome. In the present study, we targeted the urokinase plasminogen activator receptor (uPAR) with a peptide conjugated with the fluophore ICG (ICG-Glu-Glu-AE105) for optical imaging. In the first part of the study we aimed to validate ICG-Glu-Glu-AE105 for resection of the primary tumor and metastases in an orthotopic human xenograft pancreatic cancer model. In the second part of the study we aimed to investigate if fluorescent-guided imaging could locate additional metastases following conventional removal of metastasis under normal white light surgery. Our study showed that ICG-Glu-Glu-AE105 was an excellent probe for intraoperative optical imaging with a mean tumor-to-background ratio (TBR) for the primary tumor of 3.5 and a TBR for the metastases of 3.4. Further, a benefit using intraoperative fluorescent guidance yielded identification of an additional 14% metastases compared to using normal white light surgery. In 4 of 8 mice there were identified additional metastases with uPAR optical imaging compared to white light. In conclusion, the uPAR-targeted optical probe ICG-Glu-Glu-AE105 enables intraoperative optical cancer imaging, including robotic surgery, and may be a benefit during intended radical resection of disseminated pancreas cancer by finding more metastasis than with traditional white light surgery.
U2 - 10.18632/oncotarget.27220
DO - 10.18632/oncotarget.27220
M3 - Journal article
C2 - 31695839
VL - 10
SP - 6308
EP - 6316
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 59
ER -
ID: 241481785