2015
DOI: 10.1002/hed.23946
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Surgical molecular navigation with ratiometric activatable cell penetrating peptide for intraoperative identification and resection of small salivary gland cancers

Abstract: Background We evaluated the use of intraoperative fluorescence guidance by enzymatically cleavable ratiometric activatable cell-penetrating peptide (RACPPPLGC(Me)AG) containing Cy5 as a fluorescent donor and Cy7 as a fluorescent acceptor for salivary gland cancer surgery in a mouse model. Methods Surgical resection of small parotid gland cancers in mice was performed with fluorescence guidance or white light (WL) imaging alone. Tumor identification accuracy, operating time and tumor free survival were compar… Show more

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Cited by 17 publications
(15 citation statements)
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“…The advances in optical imaging technology, coupled with the development of new fluorescent probes and the increasing capability of computer software for image acquisition and analysis, have enabled FRET to elucidate molecular interactions inside living animals with improved sensitivity and spatial/temporal resolution. In particular, the development of near‐infrared fluorescence (NIRF) probes plays a vital role in real‐time imaging of dynamic molecular events in vivo . Thus, FRET imaging has a great potential for gaining insight into the function–mechanism relationship, especially for the development of drug delivery systems.…”
Section: Introductionmentioning
confidence: 99%
“…The advances in optical imaging technology, coupled with the development of new fluorescent probes and the increasing capability of computer software for image acquisition and analysis, have enabled FRET to elucidate molecular interactions inside living animals with improved sensitivity and spatial/temporal resolution. In particular, the development of near‐infrared fluorescence (NIRF) probes plays a vital role in real‐time imaging of dynamic molecular events in vivo . Thus, FRET imaging has a great potential for gaining insight into the function–mechanism relationship, especially for the development of drug delivery systems.…”
Section: Introductionmentioning
confidence: 99%
“…Diagnosis of HNSCC is often made at an advanced stage, partly due to the lack of reliable non-invasive methods to accurately identify malignant lesions [2630]. Our lab has established the use of MMP sensitive RACPPs for image-guided surgery of tumors in various animal xenograft and transgenic models of breast cancer [20, 23], pancreatic cancer [21], melanoma and HNSCC [22]. In this study, we have successfully generated oral cavity SCC in an immunocompetent rodent model as previously described [10] and used established MMP responsive ratiometric fluorescence imaging, for comparative detection of cancerous lesions using white light inspection.…”
Section: Discussionmentioning
confidence: 99%
“…The cationic fragment of the RACPP is retained at the activation site, typically within the tumor. We have previously reported the use of MMP activatable cell penetrating peptides (ACPPs) probes for image guided surgery of tumors in various animal models of breast cancer [20], pancreatic cancer[21], melanoma and head and neck xenografts[22, 23]. We have also demonstrated significant correlation of ratiometric fluorescence (Cy5:Cy7) from the MMP cleavable RACPP with tumor burden in a pancreatic tumor mouse model [21].…”
Section: Introductionmentioning
confidence: 99%
“…Initially, the Cy5 fluorophore is quenched owing to the close proximity to Cy7 but, upon cleavage, the Cy5 signal to Cy7 signal ratio increases over 40-fold 106 . The use of ratiometric imaging circumvents the problems associated with quantification using single-wavelength intensity measurements (dose-dependent uptake and PK characteristics), and the fluorophore exhibits fast activation (within 2 h) 106,138,139 .…”
Section: Targeted Fluorophore Developmentmentioning
confidence: 99%