Optical molecular imaging in oral- and oropharyngeal squamous cell carcinoma using a novel uPAR-targeting near-infrared imaging agent FG001 (ICG-Glu-Glu-AE105): An explorative phase II clinical trial.

Background: In oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC), frequent inadequate surgical margins highlight the importance of precise intraoperative identification and delineation of cancerous tissue for improving patient outcomes. Methods: A prospective, open-label, single-center, single dose, exploratory phase II clinical trial (EudraCT 2022-001361-12) to assess the efficacy of the novel uPAR-targeting near-infrared imaging agent, FG001, for intraoperative detection of OSCC and OPSCC. Macroscopic tumor detection was quantified with sensitivity and intraoperative tumor-to-background ratio (TBR). Microscopic tumor-specificity was assessed by analysis of morphological co-localization between tumor tissue, uPAR-expression, and optical signal. Blood samples were collected up to 44 hours post-injection to further characterize the pharmacokinetic profile of the agent. The trial was conducted with close safety monitoring. Results: Sixteen patients undergoing primary surgical resection were systemically administered 36 mg (n = 4), 16 mg (n = 8), or 4 mg (n = 4) of FG001 the evening prior to surgery. Intraoperatively, using a near-infrared imaging system, real-time optical imaging successfully identified all 16 tumors (sensitivity: 100%, mean TBR: 2.99 range: 2.02 - 3.95), and tumor-specificity was confirmed by histology. Clinical neck metastasis was detected with optical imaging. The maximal plasma concentrations were measured after 1 hour, and the half-life of FG001 was 12 hours. No drug-related or serious adverse events were observed. Conclusions: FG001 holds great potential for optical molecular imaging of OSCC and OPSCC. Further trials are warranted to explore FG001 for intraoperative margin delineation and as a decision-making tool.