RT Journal Article SR Electronic T1 Epidermal growth factor receptor targeted fluorescence molecular imaging for postoperative lymph node assessment in patients with oral cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.121.262530 DO 10.2967/jnumed.121.262530 A1 Jasper Vonk A1 Jaron G de Wit A1 Floris J Voskuil A1 Yang Hang Tang A1 Wouter TR Hooghiemstra A1 Matthijs D Linssen A1 Evert van den Broek A1 Jan J Doff A1 Sebastiaan AHJ de Visscher A1 Kees P Schepman A1 Bert van der Vegt A1 Gooitzen M van Dam A1 Max JH Witjes YR 2021 UL http://jnm.snmjournals.org/content/early/2021/09/15/jnumed.121.262530.abstract AB Rationale: In most oral cancer patients, surgical treatment includes resection of the primary tumor combined with the excision of lymph nodes (LN), either for staging or treatment. All LNs harvested during surgery require tissue processing and subsequent microscopic histopathological assessment to determine the nodal stage. In this study, we investigated the use of the fluorescent tracer cetuximab-800CW to discriminate between tumor-positive and tumor-negative LNs before histopathological examination. Methods: Here, we report a retrospective ad hoc analysis of a clinical trial designed for resection margin evaluation of oral squamous cell carcinoma patients (NCT02415881). Two days prior to surgery, patients were intravenously administered with 75 mg cetuximab followed by 15 mg cetuximab-800CW, an Epidermal Growth Factor Receptor (EGFR)-targeting fluorescent tracer. Fluorescence images were obtained of excised, formalin-fixed LNs and correlated with histopathological assessment. Results: Fluorescence molecular imaging of 514 LNs (61 pathologically positive nodes) can detect tumor-positive LNs ex vivo with 100% sensitivity and 86.8% specificity (AUC 0.97). In this cohort, the number of LNs that require microscopic assessment was decreased by 77.4%, without missing any metastasis. Additionally, in 7.5% of the fluorescence false-positive LNs, we identified metastases missed by standard histopathological analysis. Conclusion: Our findings suggest that EGFR-targeted fluorescence molecular imaging can aid in the detection of LN metastases in the ex vivo setting in oral cancer patients. This image-guided concept can improve the efficacy of postoperative LN examination and identify additional metastases, which safeguards appropriate postoperative therapy and may improve patient prognosis.