Paula Demétrio de Souza França1,2, Navjot Guru1, Abigail R Kostolansky1,3, Audrey Mauguen4, Giacomo Pirovano1, Susanne Kossatz1,5, Sheryl Roberts1, Marcio Abrahão2, Snehal G Patel6, Kay J Park7, Thomas Reiner8,9,10, Elizabeth Jewell6. 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 2. Department of Otorhinolaryngology and Head and Neck Surgery, Federal University of São Paulo, São Paulo, Brazil. 3. Department of Chemistry, Princeton University, Princeton, New Jersey. 4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Department of Nuclear Medicine, University Hospital Klinikum Rechts der Isar and TranslaTUM, Technical University Munich, Munich, Germany. 6. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; jewelle@mskcc.org. 9. Department of Radiology, Weill Cornell Medical College, New York, New York; and. 10. Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract
Despite efforts in prevention, cervical cancer still presents with a high worldwide incidence and remains a great problem in public health, especially in low-income countries. Screening programs, such as colposcopy with Papanicolaou testing, have greatly improved mortality rates. However, the agents currently used to delineate those lesions (topical application of acetic acid or Lugol iodine) lack specificity and sometimes can lead to unnecessary biopsies or even cervical excisions. A tool to enable in vivo histology to quickly and quantitatively distinguish between tumor, dysplastic tissue, and healthy tissue would be of great clinical interest. Methods: Here, we describe the use of PARPi-FL, a fluorescent inhibitor of poly[adenosine diphosphate-ribose]polymerase 1 (PARP1), which is a nuclear enzyme that is overexpressed in cancer when compared with the normal surrounding tissues. We exploit its use as an optical imaging agent to specifically target PARP1 expression, which was demonstrated to be higher in cervical cancer than the normal surrounding tissue. Results: After topical application of PARPi-FL on freshly excised cone biopsy samples, the nuclei of tumor cells emitted a specific fluorescent signal that could be visualized using a handheld fluorescence confocal microscope. Conclusion: This approach has the potential to improve in vivo identification of tumor cells during colposcopy examination, allowing a rapid, noninvasive, and accurate histopathologic assessment.
Despite efforts in prevention, cervical cancer still presents with a high worldwide incidence and remains a great problem in public health, especially in low-income countries. Screening programs, such as colposcopy with Papanicolaou testing, have greatly improved mortality rates. However, the agents currently used to delineate those lesions (topical application of acetic acid or Lugol iodine) lack specificity and sometimes can lead to unnecessary biopsies or even cervical excisions. A tool to enable in vivo histology to quickly and quantitatively distinguish between tumor, dysplastic tissue, and healthy tissue would be of great clinical interest. Methods: Here, we describe the use of PARPi-FL, a fluorescent inhibitor of poly[adenosine diphosphate-ribose]polymerase 1 (PARP1), which is a nuclear enzyme that is overexpressed in cancer when compared with the normal surrounding tissues. We exploit its use as an optical imaging agent to specifically target PARP1 expression, which was demonstrated to be higher in cervical cancer than the normal surrounding tissue. Results: After topical application of PARPi-FL on freshly excised cone biopsy samples, the nuclei of tumor cells emitted a specific fluorescent signal that could be visualized using a handheld fluorescence confocal microscope. Conclusion: This approach has the potential to improve in vivo identification of tumor cells during colposcopy examination, allowing a rapid, noninvasive, and accurate histopathologic assessment.
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