title: VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.
abstract: Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics.
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Chicago, IL, USA Department of Obstetrics and Gynecology, Rush University Medical Center, Chicago, IL, USA Department of Pathology, Rush University Medical Center, Chicago, IL, USA Animesh_Barua@rush.edu.
authors.forename: Animesh
authors.initials: A
authors.lastname: Barua
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Yellapa
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Bahr
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Machado
authors.affiliation: Department of Obstetrics and Gynecology, Rush University Medical Center, Chicago, IL, USA Department of Pathology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Pincas
authors.initials: P
authors.lastname: Bitterman
authors.affiliation: Department of Preventive Medicine (Biostatistics), Rush University Medical Center, Chicago, IL, USA.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Chicago, IL, USA Department of Obstetrics and Gynecology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Sameer
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Obstetrics and Gynecology, Rush University Medical Center, Chicago, IL, USA Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA.
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Abramowicz
mesh_terms: D000818:Animals; D002645:Chickens; D003287:Contrast Media; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D005260:Female; D007089:Image Enhancement / Q000379:methods*; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015203:Reproducibility of Results; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: VEGFR2-targeted imaging agent; early detection; laying hen model; ovarian cancer; ultrasound imaging