Use of Dual-Modality Antibody Imaging for Assessment of Lymph Node Metastases in Head and Neck Cancer

Surgical management of head and neck squamous cell carcinoma (HNSCC) patients often requires resection of the deep cervical lymph nodes. Fluorescence guided surgery (FGS) is a growing area of oncologic surgery that has shown promise for this purpose, however, it is limited by the signal penetration through the neck. To address this, we sought to evaluate the efficacy of the anti-EGFR antibody [¹¹¹In]panitumumab to detect metastatic lymph nodes both on preoperative imaging and intraoperatively. We hypothesized that the addition of a radiolabeled antibody would be safe and effective in detecting malignant tissue when given alone or together with the optical agent panitumumab-IRDye800CW (pan800). <b>Methods:</b> Seventeen patients were enrolled and received 5 mCi of [¹¹¹In]panitumumab with nine patients (53%) receiving [¹¹¹In]panitumumab and pan800. SPECT/CT scans were performed prior to surgical resection. Intraoperatively, patients underwent gamma tracing and the patients who received pan800 also underwent optical fluorescence imaging. Resected specimens were compared to final histopathology to determine the sensitivity and specificity of the two tracers. <b>Results:</b> No adverse events related to the [¹¹¹In]panitumumab were reported. SPECT/CT performed 3 days post-injection showed higher tumor-to-blood pool ratio compared to earlier scans (p = 0.04), and when compared to pathological assessment, could detect disease greater than 1 cm in diameter. Intraoperatively, resection of the primary tumor resulted in a significant drop in gamma counts (p < 0.001). <i>In vivo</i> detection of metastatic lymph nodes using the radiotracer was inconsistent and attributed to high background counts as patients who underwent surgery before 48 hours post-injection had significantly higher precordial counts than patients who underwent surgery after 48 hours, even when corrected for time, weight, and dose (p = 0.04). <i>Ex vivo</i>, metastatic lymph nodes had gamma counts almost twice that of benign (p < 0.0001). The separately dosed pan800 and [¹¹¹In]panitumumab showed strong co-localization within metastatic lymph nodes (R = 0.87). <b>Conclusion:</b> Intravenous infusion of [¹¹¹In]panitumumab in HNSCC patients is safe, whether administered alone or with pan800. Consistent with other studies, <i>ex vivo</i> application of the radiotracer differentiated tumor containing tissue from benign. However, intraoperative use of the radiotracer to detect metastatic lymph nodes was limited by background signal at early timepoints and signal decay at later timepoints.