Lymphoseek Demonstrates Preferential Accumulation in Tumor-Positive Sentinel Lymph Nodes

June 17, 2014 — Navidea Biopharmaceuticals Inc. announced results from a post-hoc analysis of patient data from the company’s phase III clinical trial (NEO3-06) of Lymphoseek in head and neck cancer.

The ability of Lymphoseek to localize in sentinel lymph nodes is based on its ability to target specific CD206 mannose receptor sites in macrophages, a type of immune cell that resides in high concentration in lymph nodes. In the NEO3-06 phase III study, Lymphoseek localization to lymph nodes showed a strong correlation with a full regional lymph node dissection and pathology analysis with a low false negative rate, a priority in identifying sentinel nodes. Lymphoseek was also observed to hone preferentially to pathology-positive nodes at a higher rate than pathology-negative nodes. These results suggest that Lymphoseek not only effectively targets sentinel lymph nodes but its ability to highlight tumor-positive lymph nodes may be augmented mechanistically by the recruitment of macrophages to cancer-harboring lymph nodes.

"The accurate detection of tumor-draining lymph nodes is fundamental for effective lymphatic mapping, to minimize lymph tissue removal, and to provide clinically useful information regarding potential cancer metastasis," said Francisco J. Civantos, M.D., FCS, University of Miami School of Medicine. "Approximately 75 percent of patients with stage 1 and 2 oral cavity head and neck cancer may be substantially over-treated if they are subjected to elective neck dissection, which involves surgical removal of a regional lymph node chain involving 30 to 45 lymph nodes. Receptor-targeted radiopharmaceuticals such as Lymphoseek that are designed to facilitate accurate and reliable diagnostic evaluation of specific sentinel lymph nodes can help spare patients morbidity that may result from elective neck dissection procedures."

“As a purpose-built, receptor-targeted radiopharmaceutical, Lymphoseek is designed to target and accumulate in macrophages present in tumor-draining lymphatic tissue,” said Frederick Cope, Ph.D., senior vice president and chief scientific officer of Navidea. “Tumor-positive lymph nodes recruit cells called tumor-associated macrophages, or TAMs, which are rich in CD206 receptors. The ability of Lymphoseek to specifically target and accumulate in macrophages demonstrated in this study led to localization of the product in tumor-draining pathology-positive lymph nodes that was 18 times higher than in all disease-negative lymph nodes. In the clinic, this reliable uptake of Lymphoseek into appropriate tissue allows for accurate removal and assessment of lymph nodes at highest risk of harboring occult metastases.”

The analysis, based on data from the clinical trial, evaluated 83 patients to determine whether Lymphoseek localization in pathology-positive lymph nodes was higher than its localization in pathology-negative nodes, and if those results were consistent with the overall sentinel lymph node population. Sentinel lymph nodes and/or non-sentinel lymph nodes (nodes removed in elective neck dissection, or END) were removed from patients undergoing sentinel lymph node biopsy for head and neck squamous cell carcinoma, and all lymph nodes were assessed for the presence of tumor. Intraoperative counts were obtained for all lymph nodes removed including END nodes. Average in vivo gamma counts for all lymph nodes removed indicated that the count ratio of pathology-positive nodes to pathology negative nodes was approximately 18:1 (p<0.0001). For sentinel lymph nodes only, the ratio was >2.5:1 (p<0.016). The results were presented in an oral session by Frederick Cope of Navidea Biopharmaceuticals at the 2014 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in St. Louis.

For more information: www.lymphoseek.com