title: The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55).
abstract: OBJECTIVE
  Tumour xenografts of well-discernible sizes can be examined well by molecular ultrasound. Here, we investigated whether very early breast carcinomas express sufficient levels of VEGFR2 for reliable molecular ultrasound imaging with targeted microbubbles.
  
  
  METHODS
  MCF-7 breast cancer xenografts were orthotopically implanted in nude mice (n = 26). Tumours measuring from 4 mm(3) (2 mm diameter) up to 65 mm(3) (5 mm diameter) were examined with automated 3D molecular ultrasound using clinically translatable VEGFR2-targeted microbubbles (BR55). Additionally, the relative tumour blood volume was assessed with non-targeted microbubbles (BR38). In vivo ultrasound data were validated by quantitative immunohistochemistry.
  
  
  RESULTS
  Very small lesions 2 mm in diameter showed the highest binding of VEGFR2-specific microbubbles. In larger tumours significantly less BR55 accumulated (p = 0.023). Nonetheless, binding of VEGFR2-targeted microbubbles was still high enough for imaging. The relative blood volume was comparable at all tumour sizes. Both findings were confirmed by immunohistochemistry. Additionally, a significantly enhanced number of large and mature vessels were detected with increasing tumour size (p < 0.01), explaining the decrease in VEGFR2 expression during tumour growth.
  
  
  CONCLUSIONS
  3D molecular ultrasound using BR55 is very well suited to depicting the angiogenic activity in very small breast lesions, suggesting its potential for detecting and characterising these lesions.
authors.affiliation: Institute for Experimental Molecular Imaging, RWTH-Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bzyl
authors.forename: Moritz
authors.initials: M
authors.lastname: Palmowski
authors.forename: Anne
authors.initials: A
authors.lastname: Rix
authors.forename: Susanne
authors.initials: S
authors.lastname: Arns
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Hyvelin
authors.forename: Sibylle
authors.initials: S
authors.lastname: Pochon
authors.forename: Josef
authors.initials: J
authors.lastname: Ehling
authors.forename: Simone
authors.initials: S
authors.lastname: Schrading
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
mesh_terms: D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D008321:Mammary Glands, Animal / Q000098:blood supply; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D045423:Microbubbles; D008967:Molecular Biology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism; D011237:Predictive Value of Tests; D011897:Random Allocation; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous; D018615:Ultrasonography, Doppler, Color / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2