Complete removal and negative margins are the goal of any surgical resection of primary oral cavity carcinoma. Current approaches to determine tumor boundaries rely heavily on surgeons’ expertise, and final histopathological reports are usually only available days after surgery, precluding contemporaneous re-assessment of positive margins. Intraoperative optical imaging could address this unmet clinical need. Using mouse models of oral cavity carcinoma, we demonstrated that PARPi-FL, a fluorescent PARP inhibitor targeting the enzyme PARP1/2, can delineate oral cancer and accurately identify positive margins, both macroscopically and at cellular resolution. PARPi-FL also allowed identification of compromised margins based on fluorescence hotspots, which were not seen in margin-negative resections and control tongues. PARPi-FL was further able to differentiate tumor from low-grade dysplasia. Intravenous injection of PARPi-FL has significant potential for clinical translation and could aid surgeons in assessing oral cancer margins in vivo.

完全切除和阴性切缘是任何原发性口腔癌手术切除的目标。目前确定肿瘤边界的方法在很大程度上依赖于外科医生的专业知识，最终的组织病理学报告通常只能在手术后几天才能获得，从而无法同时重新评估阳性切缘。术中光学成像可以解决这一未满足的临床需求。使用口腔癌小鼠模型，我们证明了 PARPi-FL（一种针对 PARP1/2 酶的荧光 PARP 抑制剂）可以在宏观和细胞分辨率上描绘口腔癌并准确识别阳性切缘。 PARPi-FL 还可以根据荧光热点识别受损边缘，这在边缘阴性切除和对照舌中未见。 PARPi-FL 进一步能够区分肿瘤和低度不典型增生。静脉注射 PARPi-FL 具有巨大的临床转化潜力，可以帮助外科医生在体内评估口腔癌边缘。