A Phase 2 Study of 99mTc-Tilmanocept in the Detection of Sentinel Lymph Nodes in Melanoma and Breast Cancer

Several (99m)Tc-labeled agents that are not approved by the U.S. Food and Drug Administration are used for lymphatic mapping. A new low-molecular-weight mannose receptor-based, reticuloendothelial cell-directed, (99m)Tc-labeled lymphatic imaging agent, (99m)Tc-tilmanocept, was used for lymphatic mapping of sentinel lymph nodes (SLNs) from patients with primary breast cancer or melanoma malignancies. This novel molecular species provides the basis for potentially enhanced SLN mapping reliability. In a prospectively planned, open-label phase 2 clinical study, (99m)Tc-tilmanocept was injected into breast cancer and cutaneous melanoma patients before intraoperative lymphatic mapping. Injection technique, preoperative lymphoscintigraphy (LS), and intraoperative lymphatic mapping with a handheld gamma detection probe were performed by investigators per standard practice. Seventy-eight patients underwent (99m)Tc-tilmanocept injection and were evaluated (47 melanoma, 31 breast cancer). For those whom LS was performed (55 patients, 70.5%), a (99m)Tc-tilmanocept hot spot was identified in 94.5% of LS patients before surgery. Intraoperatively, (99m)Tc-tilmanocept identified at least one regional SLN in 75 (96.2%) of 78 patients: 46 (97.9%) of 47 in melanoma and 29 (93.5%) of 31 in breast cancer cases. Tissue specificity of (99m)Tc-tilmanocept for lymph nodes was 100%, displaying 95.1% mapping sensitivity by localizing in 173 of 182 nodes removed during surgery. The overall proportion of (99m)Tc-tilmanocept-identified nodes that contained metastatic disease was 13.7%. Five procedure-related serious adverse events occurred, none related to (99m)Tc-tilmanocept. Our results demonstrate the safety and efficacy of (99m)Tc-tilmanocept for use in intraoperative lymphatic mapping. The high intraoperative localization and lymph node specificity of (99m)Tc-tilmanocept and the identification of metastatic disease within the nodes suggest SLNs are effectively identified by this novel mannose receptor-targeted molecule.