title: Biodistribution of P-selectin targeted microbubbles.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Radiology and.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Warram
authors.forename: Anna G
authors.initials: AG
authors.lastname: Sorace
authors.forename: Marshall
authors.initials: M
authors.lastname: Mahoney
authors.forename: Sharon
authors.initials: S
authors.lastname: Samuel
authors.forename: Bryant
authors.initials: B
authors.lastname: Harbin
authors.forename: Madhura
authors.initials: M
authors.lastname: Joshi
authors.forename: Amber
authors.initials: A
authors.lastname: Martin
authors.forename: Lee
authors.initials: L
authors.lastname: Whitworth
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hoyt
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003287:Contrast Media; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D019007:P-Selectin / Q000037:antagonists & inhibitors* / Q000235:genetics; D011877:Radionuclide Imaging; D013667:Technetium; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D003287:Contrast Media; D019007:P-Selectin; D013667:Technetium
keywords: Biodistribution; P-selectin; cancer; microbubbles; targeted delivery
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