PT - JOURNAL ARTICLE AU - Susanne Kossatz AU - Giacomo Pirovano AU - Paula Demétrio De Souza França AU - Arianna L. Strome AU - Sumsum P. Sunny AU - Daniella Karassawa Zanoni AU - Audrey Mauguen AU - Brandon Carney AU - Christian Brand AU - Veer Shah AU - Ravindra D. Ramanajinappa AU - Naveen Hedne AU - Praveen Birur AU - Smita Sihag AU - Ronald A. Ghossein AU - Mithat Gönen AU - Marshall Strome AU - Amritha Suresh AU - Daniela Molena AU - Moni A. Kuriakose AU - Snehal G. Patel AU - Thomas Reiner TI - PARP1 as a biomarker for early detection and intraoperative tumor delineation in epithelial cancers – first-in-human results AID - 10.1101/663385 DP - 2019 Jan 01 TA - bioRxiv PG - 663385 4099 - http://biorxiv.org/content/early/2019/06/14/663385.short 4100 - http://biorxiv.org/content/early/2019/06/14/663385.full AB - Major determining factors for survival of patients with oral, oropharyngeal, and esophageal cancer are early detection, the quality of surgical margins, and the contemporaneous detection of residual tumor. Intuitively, the exposed location at the epithelial surface qualifies these tumor types for utilization of visual aids to assist in discriminating tumor from healthy surrounding tissue. Here, we explored the DNA repair enzyme PARP1 as imaging biomarker and conducted optical imaging in animal models, human tissues and as part of a first-in-human clinical trial. Our data suggests that PARP1 is a quantitative biomarker for oral, oropharyngeal, and esophageal cancer and can be visualized with PARPi-FL, a fluorescently labeled small molecule contrast agent for topical or intravenous delivery. We show feasibility of PARPi-FL-assisted tumor detection in esophageal cancer, oropharyngeal and oral cancer. We developed a contemporaneous PARPi-FL topical staining protocol for human biospecimens. Using fresh oral cancer tissues within 25 min of biopsy, tumor and margin samples were correctly identified with >95% sensitivity and specificity without terminal processing. PARPi-FL imaging can be integrated into clinical workflows, potentially providing instantaneous assessment of the presence or absence of microscopic disease at the surgical margin. Additionally, we showed first-in-human PARPi-FL imaging in oral cancer. In aggregate, our preclinical and clinical studies have the unifying goal of verifying the clinical value of PARPi-FL-based optical imaging for early detection and intraoperative margin assignment.