We propose to synthesize and test a receptor-binding radiopharmaceutical, [99mTc]DTPA-mannosyl-dextran (TcDMD), for sentinel node imaging of breast cancer and melanoma. TcDMD consists of a dextran backbone to which we attach mannose and DTPA. The mannose moieties bind to a receptor that is specific to the cell surface of macrophages. We will optimize the performance of TcDMD for the following properties: l) rapid clearance from the injection site, 2) high retention within the lymph vessel, 3) rapid, complete, and sustained uptake by the sentinel lymph node, 4) low uptake by remaining regional and distal lymph nodes, 5) low radiation absorption and high biological safety, and 6) convenient, rapid, and stable technetium-99m labeling with high radiochemical purity. [99mTc]Antimony-trisulfide colloid (TcATC) and filtered colloids do not exhibit these properties. We will test the hypothesis that the following five imaging properties of our proposed sentinel node imaging agent, [99mTc]DTPA-mannosyl-dextran, are superior to TcATC: l) injection site clearance, 2) percentage-of-injected dose, 3) time-to-peak in the sentinel node, 4) sentinel node retention time, and 5) absorbed radiation dose of the target organ. These properties will be measured during sentinel node imaging of TcDMD and TcATC in Sinclair swine, a native model of melanoma that exhibits lymph node metastasis. The radiopharmaceuticals currently employed for were not designed for sentinel node imaging. We propose that an agent optimized specifically for the detection of the sentinel node should provide a significantly higher level of radiopharmaceutical and imaging performance and therefore increase detection efficiency. The overall result will be a more cost effective procedure for staging women with breast cancer and patients suffering from melanoma.
|Mendez, Jeanette; Wallace, Anne M; Hoh, Carl K et al. (2003) Detection of gastric and colonic sentinel nodes through endoscopic administration of 99mTc-DTPA-mannosyl-dextran in pigs. J Nucl Med 44:1677-81|
|Hoh, Carl K; Wallace, Anne M; Vera, David R (2003) Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran . Nucl Med Biol 30:457-64|
|Vera, D R; Wallace, A M; Hoh, C K (2001) [(99m)Tc]MAG(3)-mannosyl-dextran: a receptor-binding radiopharmaceutical for sentinel node detection. Nucl Med Biol 28:493-8|
|Vera, D R; Wallace, A M; Hoh, C K et al. (2001) A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. J Nucl Med 42:951-9|