RT Journal Article SR Electronic T1 PARP1 as a biomarker for early detection and intraoperative tumor delineation in epithelial cancers – first-in-human results JF bioRxiv FD Cold Spring Harbor Laboratory SP 663385 DO 10.1101/663385 A1 Susanne Kossatz A1 Giacomo Pirovano A1 Paula Demétrio De Souza França A1 Arianna L. Strome A1 Sumsum P. Sunny A1 Daniella Karassawa Zanoni A1 Audrey Mauguen A1 Brandon Carney A1 Christian Brand A1 Veer Shah A1 Ravindra D. Ramanajinappa A1 Naveen Hedne A1 Praveen Birur A1 Smita Sihag A1 Ronald A. Ghossein A1 Mithat Gönen A1 Marshall Strome A1 Amritha Suresh A1 Daniela Molena A1 Moni A. Kuriakose A1 Snehal G. Patel A1 Thomas Reiner YR 2019 UL http://biorxiv.org/content/early/2019/06/14/663385.abstract 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.