1. Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides
- Author
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Hingorani, Dina V, Lemieux, Aaron J, Acevedo, Joseph R, Glasgow, Heather L, Kedarisetty, Suraj, Whitney, Michael A, Molinolo, Alfredo A, Tsien, Roger Y, and Nguyen, Quyen T
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Cancer ,Digestive Diseases ,Dental/Oral and Craniofacial Disease ,Rare Diseases ,4-Nitroquinoline-1-oxide ,Animals ,Carcinogens ,Carcinoma ,Squamous Cell ,Cell-Penetrating Peptides ,Disease Models ,Animal ,Female ,Fluorescence ,Mice ,Mice ,Inbred C57BL ,Mouth Neoplasms ,Sensitivity and Specificity ,Ratiometricfluorescence imaging ,Matrix metalloproteinase ,Enzyme responsive ,Carcinogen-induced head and neck ,squamous cell carcinoma ,In vivo ,Carcinogen-induced head and neck squamous cell carcinoma ,Dentistry ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
ObjectivesRatiometric 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.MethodsWild-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.ResultsIn 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
- Published
- 2017