Fluorescent-Labeled Tilmanocept for Sentinel Lymph Node Identification in Rectal Cancer during Robotic Surgery: A Preclinical Study in the Porcine Model

The management of lateral pelvic lymph nodes in locally advanced lower rectal cancer remains controversial. The sentinel lymph node (SLN) mapping can potentially enhance patient selection for lateral pelvic lymph node dissection. The current mapping agent, indocyanine green dye cannot be externally imaged prior to surgery and is not retained after entering the SLN. This study evaluated the ability of tilmanocept, a receptor-specific SLN mapping agent, to provide preoperative PET cross-sectional imaging and sustained intraoperative fluorescence images during rectal cancer surgery. Tilmanocept was labeled with gallium-68, technetium-99m, and a near-infrared fluorophore. Four pigs were studied. Tilmanocept was injected into the submucosal layer of the rectal wall followed one hour later by PET/CT images of the pelvis, which identified ten SLNs, one of which was a pudendal artery regional SLN. Approximately forty-five hours after administration, SLN dissection was guided by fluorescence imaging during robotic surgery. The tenth SLN was excised by open surgery. The radioactive and fluorescent intensities of all ten excised SLNs were significantly higher than the non-SLNs. The ability of dual-labeled tilmanocept to provide preoperative SLN imaging can potentially reduce morbidity and operation time by identifying patients who will not require lateral pelvic lymph node dissections.