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Near-Infrared Fluorescent Albumin for Intraoperative Imaging (BIDMC 815)
Category: Medical Imaging
KeyWords: Surgery; Cancer; Vascular/Thrombosis;
BIDMC ID: 815
Abstract:
Background:
Intraoperative imaging of surgical patients has important applications, including Sentinel Lymph Node (SNL) mapping, mapping of the vasculature and determining sites of bleeding.
The underlying hypothesis of SLN mapping is that the first lymph node to receive lymphatic drainage from a tumor site provides accurate staging of cancer, and can guide regional and systematic treatment. From a clinical standpoint, SLN mapping and dissection have revolutionized the assessment of nodal status, particularly for melanoma and breast cancers.
Intraoperative SNL mapping is currently performed using a combination of radioactive tracers and blue dyes. Radioactive tracers emit mid-energy gamma rays within the body, and the blue dyes require surgical exploration to find the lymph node. Due to technical limitations imposed by radiotracers and vital blue dyes, cancers arising in skin are much more amenable, at present, to SNL mapping and dissection than are visceral cancers such as pancreatic or colorectal cancers. In addition there is a need for imaging agents that permit imaging of the lymphatic system and vasculature over extended periods of time without causing toxic reactions in patients. Many common imaging agents qiuqkly degrade in the body, and therefore are only useful for imaging over short periods of time, and the difficulty of longer lasting agents is toxicity. Finally this invention can be used to identify the location and size of blood vessels and to determine the exact site of bleeding, another critical unmet need.
Invention:
The invention is a highly substituted, near-infrared fluorescent derivative of human albumin that can be used intraoperatively to generate contrast in blood vessels and to find sentinel lymph nodes. When injected intravenously, such a compound, in conjugation with an appropriate near-infrared fluorescence imaging system, such as subject of patent application PCT/US03/29368 “medical imaging systems”, can provide optical guidance to the surgeon regarding vessel location, size, depth and geometry. It can also be used to determine the exact site of bleeding in an otherwise bloody field. This compound has a long half life, thus enables imaging over longer periods of time. The composition in combination with an intraoperative NIR emission imaging system can provide SLN mapping for all types of human solid cancers.
Inventor: John V. Frangioni, M.D., Ph.D. and Shunsuke Onishi, M.D., Ph.D.
Commercial Opportunity:
Commercial opportunities include mapping the lymphatic system or the vasculature of patients, real time mapping of sentinel lymph nodes and intraoperative identification of blood vessels and sites of bleeding.
Competitive Advantages:
Unlike available agents, which either quickly degrade in the body or are toxic, serum albumin is non-toxic and has a long half-life under physiological conditions. The modified albumin dyes of the invention survive for extended periods of time in the body, without engendering significant toxic reactions.
The compositions described here can be monitored through the skin to identify the sentinel node, avoiding or minimizing surgical exploration.
In addition, this agent shows high retention in the vasculature, yielding higher contrast between vasculature and tissue compared to small molecule near-infrared fluorophores.
Related Publications:
*IRDye78 Conjugates for Near-Infrared Fluorescence Imaging”, Mol. Imaging, 2002; 1:354-364.
*Functional Near-Infrared Fluorescence Imaging for Cardiac Surgery and Targeted Gene Therapy”, Mol. Imaging, 2002; 1: 365-377.
State of Development:
*The optical properties of the compound have been characterized and optimized. *Experiments have shown NIR albumin efficiency for intravascular mapping. *Identification of sites of bleeding and detection of lymph nodes in
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