Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides.

Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides.

Oral Oncol. 2017 Aug;71:156-162

Authors: Hingorani DV, Lemieux AJ, Acevedo JR, Glasgow HL, Kedarisetty S, Whitney MA, Molinolo AA, Tsien RY, Nguyen QT

Abstract
OBJECTIVES: Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model.
METHODS: Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence.
RESULTS: In an initial study we found that at week 21 nearly all mice (13/14) had oral cavity lesions, of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade lesions were identifiable with white light reflectance and RACPP Cy5:Cy7 ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for RACPP detection was 0.97 (95% Confidence interval (CI)=0.92-1.02, p<0.001), sensitivity=89%, specificity=100%. In a follow up study, oral cavity lesions generated by 4NQO were imaged and histologically analyzed at weeks 16, 18 and 21. In this study we showed that RACPP-fluorescence detection positively identified 15 squamous cell carcinomas (in 6 separate mice) that were poorly visible or undetectable by white light reflectance.
CONCLUSIONS: RACPP ratiometric fluorescence can be used to accurately detect carcinogen-induced carcinoma in immunocompetent mice that are poorly visible or undetectable by white light reflectance.

PMID: 28688684 [PubMed - in process]

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