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
The intraoperative lymphaticmapping (ILM) concept, based on evidence that colored agents injected into tissues leads to tracing of the agents into lymphatic structures, has carried over from observations dating back to the 1920s. The modern concept of using the pathological status of the lymph nodes to decide whether regional lymphatic clearance should be done was clearly articulated by Cabanas in 1977. Refinement of the concept as it would be reduced to a practical methodology of lymph node identification both in Europe and the United States began in earnest in the 1990s. Development of the application of sentinel node mapping has been built upon the concept of an anatomic/biologic nexus between the solid tumor bed and the immediate versus the distal lymphatic structures. It is the “biological proximity” that defines the probability of found disease in the adnexa, between the tumor bed and the lymphatic structures. It is inferred that the probability of disseminated disease in any lymphatic anatomy is highest when anatomic or biologic nexuses actually exist, as opposed to the lack of any anatomic nexuses where disease dissemination probabilities in lymphatic structures are lowest. To date, agents that have been employed in this procedure bear only simple designs that utilize simple physiologic pulse/draining of the lymphatics and provide no specificity for targeting the lymphatic tissue of interest. We present here patient results of three Phase III studies in head/neck squamous cell carcinoma, breast cancer, and melanoma where a novel 99mTc-labeled receptor targeted agent (99mTc-tilmanocept) not only out performed standard of care agents, but lent itself to remarkable concordance of intraoperative nodal localization with preoperative SPECT/CT imaging. The conclusion of these studies is that 99mTc-tilmanocept provides higher localization rates, degree of localization, lower failed detection rates, and reliable concordance between imaging and intraoperative findings. This work was supported by Neoprobe Corporation, Dublin, OH 43017 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2700. doi:1538-7445.AM2012-2700
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