Authors: Paula Demetrio de Souza Franca, Navjot Guru, Abigail R. Kostolansky, Audrey Mauguen, Giacomo Pirovano, Susanne Kossatz, Sheryl Roberts, Marcio Abrahao, Snehal G. Patel, Thomas Reiner and Elizabeth Jewell
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 and/or Lugol's 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 and healthy tissue would be of great clinical interest. Here we describe the use of PARPi-FL, a fluorescent imaging agent that targets PARP1, a nuclear enzyme that is overexpressed in cancer when compared to 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 when compared to the normal surrounding tissue. After its topical application on freshly excised cone biopsies, the nuclei of tumor cells emitted a specific fluorescent signal that could be visualized using a hand-held fluorescence confocal microscope. This approach has the potential to improve in vivo identification of tumor cells during colposcopy examination allowing a rapid, non-invasive, and accurate histopathological assessment.
Keywords: Fluorescence guided surgery; Molecular Imaging; Oncology: GYN; PARP1; PARPi-FL; cervical cancer.