title: Relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent and the level of VEGFR2 expression in an in vivo breast cancer model.
abstract: OBJECTIVE
  The aim of this study was to characterize the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasonographic contrast agent (UCA) and VEGFR2 expression in tumor vasculature of breast cancer.
  
  
  METHODS
  67NR breast cancer tumors implanted in mice were evaluated in vivo with both VEGFR2-targeted and nontargeted UCAs, and a high-frequency ultrasound system. A bolus of the UCA was injected and allowed to circulate for 4 minutes to allow binding of targeted microbubbles. After that, 2 sets of images before and after a high-power ultrasonic destruction sequence were acquired. The average video intensity of predestruction and postdestruction images was measured and used as a relative measure of retention of the UCA in the tumor. Levels of VEGFR2 expression and tumor vascular density were quantified by immunohistochemical staining and compared with retention of the VEGFR2-targeted UCA.
  
  
  RESULTS
  Retention of VEGFR2-targeted microbubbles in tumors was significantly higher than retention of nontargeted microbubbles (mean +/- SD, 47.75+/-9.85 versus 18.5+/-5.46 dB; P< .001). Retention of the VEGFR2-targeted UCA was found to correlate with the level of VEGFR2 expression in the studied tumors (r(2)=0.41). In contrast, retention of the nontargeted UCA was not correlated with the level of VEGFR2 expression (r(2)=0.08). Furthermore, retention of the VEGFR2-targeted UCA was not correlated with the level of tumor vascularity.
  
  
  CONCLUSIONS
  The magnitude of the molecular ultrasonographic signal from a VEGFR2-targeted UCA retained by tissue correlates with VEGFR2 expression. These results validate the use of molecular ultrasonography for in vivo detection and quantification of VEGFR2 expression in this breast cancer model.
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Debbie J
authors.initials: DJ
authors.lastname: Lee
authors.forename: Andrej
authors.initials: A
authors.lastname: Lyshchik
authors.forename: Jessica
authors.initials: J
authors.lastname: Huamani
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Hallahan
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Fleischer
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000378:metabolism*; D016503:Drug Delivery Systems; D008297:Male; D051379:Mice; D045423:Microbubbles; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2