Biodistribution of P-selectin targeted microbubbles

J Drug Target. 2014 Jun;22(5):387-94. doi: 10.3109/1061186X.2013.869822. Epub 2014 Apr 14.

Abstract

Purpose: To evaluate binding of P-selectin targeted microbubbles (MB) in tumor vasculature; a whole-body imaging and biodistribution study was performed in a tumor bearing mouse model.

Methods: Antibodies were radiolabeled with Tc-99 m using the HYNIC method. Tc-99 m labeled anti-P-selectin antibodies were avidin-bound to lipid-shelled, perfluorocarbon gas-filled MB and intravenously injected into mice bearing MDA-MB-231 breast tumors. Whole-body biodistribution was performed at 5 min (n = 12) and 60 min (n = 4) using a gamma counter. Tc-99 m-labeled IgG bound IgG-control-MB group (n = 12 at 5 min; n = 4 at 60 min), Tc-99 m-labeled IgG-control-Ab group (n = 5 at 5 min; n = 3 at 60 min) and Tc-99 m-labeled anti P-selectin-Ab group (n = 5 at 5 min; n = 3 at 60 min) were also evaluated. Planar gamma camera imaging was also performed at each time point.

Results: Targeted-MB retention in tumor (60 min: 1.8 ± 0.3% ID/g) was significantly greater (p = 0.01) than targeted-MB levels in adjacent skeletal muscle at both time points (5 min: 0.7 ± 0.2% ID/g; 60 min: 0.2 ± 0.1% ID/g) while there was no significant difference (p = 0.17) between muscle and tumor retention for the IgG-control-MB group at 5 min.

Conclusions: P-selectin targeted MBs were significantly higher in tumor tissue, as compared with adjacent skeletal tissue or tumor retention of IgG-control-MB.

Keywords: Biodistribution; P-selectin; cancer; microbubbles; targeted delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacokinetics*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Monoclonal / therapeutic use
  • Cell Line, Tumor
  • Contrast Media
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / diagnostic imaging
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Mice, Nude
  • Microbubbles*
  • P-Selectin / antagonists & inhibitors*
  • P-Selectin / genetics
  • Radionuclide Imaging
  • Technetium
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Contrast Media
  • P-Selectin
  • Technetium