A phase 2 study of (99m)Tc-tilmanocept in the detection of sentinel lymph nodes in melanoma and breast cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Minimally invasive sentinel lymph node mapping of the pig colon with Lymphoseek.

BACKGROUND: Minimally invasive surgery and sentinel node mapping are being utilized increasingly in colon cancer surgery. Making these techniques efficient and easy to perform will be essential for the future of this and other gastrointestinal operations. The purpose of this study was to test a new laparoscopic gamma detection probe for minimally invasive sentinel node mapping of the colon, while utilizing Lymphoseek, a radiopharmaceutical specifically designed for sentinel lymph node (SLN) detection. METHODS: Eight anesthetized pigs received an endoscopic co-injection of Lymphoseek and Isosulfan Blue in the colon. The laparoscopic gamma detector, inserted via a 12-mm trocar, was used to identify radioactive sentinel lymph nodes. The reliability of the side-viewing probe was tested using a radioactive source. All blue and radioactive lymph nodes were excised and the signal-to-background ratio (S/B) and percent of injected dose (%ID) were measured. RESULTS: The probe was easy to maneuver and led to efficient visualization of the radioactive node. The side port allowed for better distinction between injection site scatter and sentinel node activity. The reliability of the probe was validated by an identification rate of 97%. At least one SLN was detected for each pig; two SLNs were detected in two pigs. All SLNs were stained blue. The SLN S/B ranged from 38 to 315 and the %ID ranged from 0.06% to 2.01%. Sentinel nodes were found within 10 minutes. CONCLUSIONS: Minimally invasive sentinel node mapping with the radiopharmaceutical Lymphoseek and a side-viewing gamma detector yielded high S/B and directionality for accurate mapping of gastrointestinal sentinel lymph nodes within minutes of radiotracer administration.