Abstract 5231: Tilmaocept: A novel biotargeted agent for enhanced intraoperative discrimination of sentinel lymph nodes in breast cancer, melanoma, and head & neck SCC

Abstract

Sentinel lymph node (SLN) mapping and identification is a primary component of surgical therapies for breast cancers, melanomas, pediatric soft tissue sarcomas, and certain other cancers. The current standard of care for identifying SLNs to inject into a tumor (or near a tumor) a blue dye (often called “vital blue dye”), of which several are available, in conjunction with a radiolabeled (99mTc) tracer, available as either a technetium sulfur colloid or as a technetium labeled albumin formulation. The exact formulations used vary, especially between those used in the United States and Europe. All such compounds are effectively agents of passive transport in the lymphatic ducts and are “inert” with regard to any biomarker recognition specificity. Allegedly, such agents move passively from the tumor/tumor basin into lymph nodes with a presumptive tumor-node anatomic nexus and the nodes are elucidated as blue and/or radioactive, the former based on excision line-of-sight, the latter based on intraoperative evaluation with a gamma-detecting probe. But because such components do not bear any specificity, that is, bind or accumulate lymph nodes bearing targets, they either remain static at the injection site and/or quickly drain away, reducing their real-time clinical effectiveness. A novel 99mTc-labeled, prospectively designed, low Mr molecule (99mTc DTPA Mannosyl Dextran; Tilmanocept) targeted as a ligand for the mannose binding receptor (MBR) of lymphatic reticuloendothelial cells and intended for real-time intraoperative gamma mapping of tumor-lymphatic nexuses has been synthesized and clinically tested in Phase 3 clinical studies in breast cancer and melanoma. The results of the development process and clinical testing indicate: 1) The prospective molecular designs resulted in safety and clinical performance characteristics that provided times from agent injection to patient evaluation that were significantly reduced compared to currently applied 99mTc-labeled agents; and 2) The specificity, sensitivity, and performance with regard to anatomic localization, false negative rates, and receptor retention exceed those of other colorimetric and 99mTc-labeled agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5231. doi:10.1158/1538-7445.AM2011-5231