Molecular targeting of lymph nodes with L-selectin ligand-specific US contrast agent: A feasibility study in mice and dogs

PURPOSE: To evaluate the feasibility of using intravenously administered L-selectin ligand-specific polymer-stabilized air-filled microparticles (MPs) for active targeting of peripheral lymph nodes under normal conditions in animal models. MATERIALS AND METHODS: L-selectin ligand-specific MPs and two control substances (immunoglobulin M-isotype MPs and native MPs) were each administered in three conscious mice as a single intravenous bolus injection (1.4 x 10(7) MPs/kg)(.) All mice were sacrificed 30 minutes after administration. Lymph nodes (cervical, inguinal, axillary, popliteal, mesenteric), spleen (positive control), and kidney (blood pool control) were removed and examined for MP-related stimulated acoustic emission (SAE) signals by using harmonic color Doppler ultrasonography (US) in a tank containing degassed water. A second experiment was performed in six anesthetized beagel dogs by using the same MP formulation. Each of the MP formulations was administered in two anesthetized dogs as a single intravenous bolus injection (1 x 10(7) MPs/kg). The popliteal lymph nodes, spleen (positive control), and kidney (blood pool control) were examined in vivo with US for MP-related SAE signals 30 minutes after administration. Fisher exact test for the one-side alternative was used for mouse data analysis. RESULTS: The lymph nodes of all mice (P = .05) and the popliteal lymph nodes of both dogs treated with L-selectin ligand-specific MPs showed clear MP-related SAE signals, whereas the lymph nodes of all mice and the popliteal lymph nodes of four dogs that received the control substances did not show any SAE signals. CONCLUSIONS: Use of an intravenously administered L-selectin ligand-specific US contrast agent is feasible for active lymph node targeting in mice and dogs. (C) RSNA, 2004.