Surgical Guidance of Head and Neck Squamous Cell Carcinoma enabled by a c-MET targeting fluorescent probe cMBP-ICG

ImportanceHead and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy which is associated with subtle local invasion and metastasis. Near-infrared (NIR) fluorescence-guided surgical precise resection of the tumor margin and potential metastasis has been appealing. ObjectiveTo determine whether a peptide-based NIR fluorescence dye, which can be administered via topical application and target tumor tissue via c-MET binding, can improve discrimination of HNSCC from normal tissue. DesignA nonrandomized controlled trial was conducted between March 2021 and February 2022 at Shanghai Ninth Peoples Hospital, China. Study participants were blinded for subjective measurements. SettingExploratory, single-center, open-label, dose-escalation ParticipantsConsecutive Asian individuals with clinically suspicious, primary or recurrent HNSCC, who were scheduled for standard-of-care surgery with curative intent, were enrolled. InterventionsEnrolled patients underwent in vivo fluorescence imaging before surgery, and ex vivo fluorescence imaging was performed on intraoperative specimens using 2.5 M or 5.0 M topical applicated fluorescent probes. Main Outcomes and MeasuresPrimary analysis compared mean fluorescence intensity (MFI, total fluorescence signal divided by the total number of pixels within the region of interest) of tumor and peritumoral normal tissue. Possible tumor-to-background ratios (TBR, ratio of MFI of tumor over peritumoral normal tissues) may range from 2 to 4. ResultsTen patients (1 female [10%], age = 59.4 {+/-} 12.6 years old) were enrolled. Ex vivo imaging with 5.0 M fluorescence prob demonstrated TBR of 2.71 {+/-} 0.7, with 2.5 M fluorescence prob demonstrated TBR of 3.11 {+/-}1.2. To discriminate tumor from normal tissue with MFI, the area under the curve (AUC) was 0.88 (95% CI-0.88 to 1.0) for the 5.0 M group, and 0.65 (95% CI 0.53 to 0.83) for the 2.5 M group. Conclusions and RelevanceThis trial demonstrates that topical application of tumor targeting fluorescence probe can differentiate tumor and outlining tumor margins. Further research is currently underway to estimate whether this probe is potent in guiding biopsy and surgical procedure, and assisting long-term follow-up postoperatively. Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2200058058