New approaches to lymphatic imaging.

Accurate imaging of the lymphatic system can aid in cancer staging, optimize surgical procedures to reduce lymphedema, and may one day be a means of delivering intralymphatic therapy. The Sentinel Lymph Node (SLN) concept has been pivotal in driving new imaging techniques. Metastasis to a SLN is a critical indicator of advanced disease. However, presently, few tools are available for imaging the lymphatics, and even fewer are available for locating the SLN for biopsy. Recently, new macromolecular agents, including gadolinium-labeled dendrimers, fluorescent quantum dots, and fluorescently-labeled immunoglobins, have been used to image the lymphatics and SLN with MRI and optical techniques, and new fluorescent nanoparticles such as upconverting nanocrystals are potential future agents. Additionally, multi-modality probes combining two modalities such as optical/MR dendrimers have been designed to provide both preoperative imaging, and intraoperative guidance during lymph node resections. These probes can map the lymphatic system for maximal therapeutic benefit while minimizing complications such as lymphedema. Advances in the understanding of the molecular mechanisms of lymphangiogenesis and lymphatic spread of tumors offer the opportunity for more targeted imaging of the lymphatic system. Additionally, these imaging agents could be used as powerful research tools for tracking immunological cells and monitoring the immune response as well as providing the means to deliver lymphatic-targeted therapies. The future holds great promise for the translation of these methods to the clinic.