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

Radiology. 2004 Jun;231(3):667-73. doi: 10.1148/radiol.2313030425. Epub 2004 Apr 29.

Abstract

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 beagle 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.

Conclusion: Use of an intravenously administered L-selectin ligand-specific US contrast agent is feasible for active lymph node targeting in mice and dogs.

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / administration & dosage
  • Antibody Specificity
  • Contrast Media*
  • Dogs
  • Feasibility Studies
  • Female
  • Immunoglobulin M / immunology
  • Immunohistochemistry
  • In Vitro Techniques
  • Injections, Intravenous
  • L-Selectin / analysis
  • L-Selectin / immunology*
  • Lymph Nodes / diagnostic imaging*
  • Lymph Nodes / immunology
  • Male
  • Mice
  • Microbubbles*
  • Polymers
  • Ultrasonography, Doppler, Color

Substances

  • Antibodies, Monoclonal
  • Contrast Media
  • Immunoglobulin M
  • Polymers
  • L-Selectin