@article {Kossatz663385, author = {Susanne Kossatz and Giacomo Pirovano and Paula Dem{\'e}trio De Souza Fran{\c c}a and Arianna L. Strome and Sumsum P. Sunny and Daniella Karassawa Zanoni and Audrey Mauguen and Brandon Carney and Christian Brand and Veer Shah and Ravindra D. Ramanajinappa and Naveen Hedne and Praveen Birur and Smita Sihag and Ronald A. Ghossein and Mithat G{\"o}nen and Marshall Strome and Amritha Suresh and Daniela Molena and Moni A. Kuriakose and Snehal G. Patel and Thomas Reiner}, title = {PARP1 as a biomarker for early detection and intraoperative tumor delineation in epithelial cancers {\textendash} first-in-human results}, elocation-id = {663385}, year = {2019}, doi = {10.1101/663385}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2019/06/14/663385}, eprint = {https://www.biorxiv.org/content/early/2019/06/14/663385.full.pdf}, journal = {bioRxiv} }