Ratiometric Activatable Cell-Penetrating Peptides Label Pancreatic Cancer, Enabling Fluorescence-Guided Surgery, Which Reduces Metastases and Recurrence in Orthotopic Mouse Models View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-06

AUTHORS

Cristina A. Metildi, Csilla N. Felsen, Elamprakash N. Savariar, Quyen T. Nguyen, Sharmeela Kaushal, Robert M. Hoffman, Roger Y. Tsien, Michael Bouvet

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the efficacy of using matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9)-cleavable ratiometric activatable cell-penetrating peptides (RACPPs) conjugated to Cy5 and Cy7 fluorophores to accurately label pancreatic cancer for fluorescence-guided surgery (FGS) in an orthotopic mouse model. METHODS: Orthotopic mouse models were established using MiaPaCa-2-GFP human pancreatic cancer cells. Two weeks after implantation, tumor-bearing mice were randomized to conventional white light reflectance (WLR) surgery or FGS. FGS was performed at far-red and infrared wavelengths with a customized fluorescence-dissecting microscope 2 h after injection of MMP-2 and MMP-9-cleavable RACPPs. Green fluorescence imaging of the GFP-labeled cancer cells was used to assess the effectiveness of surgical resection and monitor recurrence. At 8 weeks, mice were sacrificed to evaluate tumor burden and metastases. RESULTS: Mice in the WLR group had larger primary tumors than mice in the FGS group at termination [1.72 g ± standard error (SE) 0.58 vs. 0.25 g ± SE 0.14; respectively, p = 0.026). Mean disease-free survival was significantly lengthened from 5.33 weeks in the WLR group to 7.38 weeks in the FGS group (p = 0.02). Recurrence rates were lower in the FGS group than in the WLR group (38 vs. 73 %; p = 0.049). This translated into lower local and distant recurrence rates for FGS compared to WLR (31 vs. 67 for local recurrence, respectively, and 25 vs. 60 % for distant recurrence, respectively). Metastatic tumor burden was significantly greater in the WLR group than in the FGS group (96.92 mm(2) ± SE 52.03 vs. 2.20 mm(2) ± SE 1.43; respectively, χ (2) = 5.455; p = 0.02). CONCLUSIONS: RACPPs can accurately and effectively label pancreatic cancer for effective FGS, resulting in better postresection outcomes than for WLR surgery. More... »

PAGES

2082-2087

Identifiers

URI

http://scigraph.springernature.com/pub.10.1245/s10434-014-4144-1

DOI

http://dx.doi.org/10.1245/s10434-014-4144-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017277754

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25319581


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302 https://www.grid.ac/institutes/grid.417448.a schema:alternateName AntiCancer (United States)
303 schema:name AntiCancer, Inc, San Diego, CA, USA
304 Department of Surgery, University of California San Diego, San Diego, CA, USA
305 Moores Cancer Center, University of California San Diego, San Diego, CA, USA
306 rdf:type schema:Organization
 




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