title: Targeted contrast-enhanced ultrasound imaging of angiogenesis in an orthotopic mouse tumor model of renal carcinoma.
abstract: Previous studies have reported that microbubbles bearing targeting ligands to molecular markers of angiogenesis can be successfully detected by ultrasound imaging in various animal models of solid cancer. In the present study, we sought to investigate the activity of microbubbles targeted to vascular endothelial growth factor receptor 2 (VEGFR2) in an orthotopic model of renal cell carcinoma (RCC). Microbubbles conjugated to an anti-VEGFR2 antibody (MBV) were compared with microbubbles conjugated to an isotype control antibody (MBC) or naked microbubbles (MBN). An orthotopic mouse model of human RCC was established by surgically implanting an established tumor within the renal capsule in mice. Tumor growth and blood flow were verified by B-mode and color Doppler ultrasound imaging. VEGFR2 expression within the tumor and renal parenchyma was detected by immunohistochemistry. The duration of contrast enhancement of MBV was much longer than those of MBN and MBC when assessed over 10 min. The baseline-subtracted contrast intensity within the tumor was higher for MBV than for MBC and MBN (p < 0.01). Additionally, the contrast intensity for MBV was significantly higher in the tumor region than in normal parenchyma (p < 0.01). Microbubbles targeting VEGFR2 exhibit suitable properties for imaging angiogenesis in orthotopic models of renal cell carcinoma, with potential applications in life science research and clinical medicine.
authors.affiliation: Department of Ultrasound Diagnostics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Ultrasound Diagnostics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Ninghua
authors.initials: N
authors.lastname: Fu
authors.affiliation: Department of Pharmacological Study, Origin Biosciences, Nanjing, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmacological Study, Origin Biosciences, Nanjing, Jiangsu, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Ultrasound Diagnostics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Ultrasound Diagnostics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Ultrasound Diagnostics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. Electronic address: yb12yx@hotmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D018615:Ultrasonography, Doppler, Color; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Contrast agent; Contrast pulse sequence; Microbubbles; Molecular imaging; Nude mouse; Orthotopic; Renal clear cell carcinoma; Targeted ultrasound; Vascular endothelial growth factor receptor 2