Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents

Yong Gao; Christopher Hernandez; Hai-Xia Yuan; Jacob Lilly; Pavan Kota; Haoyan Zhou; Hanping Wu; Agata A Exner

doi:10.1016/j.nano.2017.06.001

Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents

Nanomedicine. 2017 Oct;13(7):2159-2168. doi: 10.1016/j.nano.2017.06.001. Epub 2017 Jun 9.

Authors

Yong Gao¹, Christopher Hernandez², Hai-Xia Yuan³, Jacob Lilly⁴, Pavan Kota⁵, Haoyan Zhou⁶, Hanping Wu⁷, Agata A Exner⁸

Affiliations

¹ Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China; Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: yxg306@case.edu.
² Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: Cxh404@case.edu.
³ Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: haixiayuan75@163.com.
⁴ Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: Jacob.Lilly@case.edu.
⁵ Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: Pavan.kota@case.edu.
⁶ Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: Hxz143@case.edu.
⁷ Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: hanping.wu@case.edu.
⁸ Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, USA. Electronic address: agata.exner@case.edu.

PMID: 28603079
DOI: 10.1016/j.nano.2017.06.001

Abstract

Ultrasound is frequently utilized in diagnosis of gynecologic malignancies such as ovarian cancer. Because epithelial ovarian cancer (EOC) is often characterized by overexpression of cancer antigen 125 (CA-125), ultrasound contrast agents able to target this molecular signature could be a promising complementary strategy. In this work, we demonstrate application of CA-125-targeted echogenic lipid and surfactant-stabilized nanobubbles imaged with standard clinical contrast harmonic ultrasound for imaging of CA-125 positive OVCAR-3 tumors in mice. Surface functionalization of the nanobubbles with a CA-125 antibody achieved rapid significantly (P < 0.05) enhanced tumor accumulation, higher peak ultrasound signal intensity and slower wash out rates in OVCAR-3 tumors compared to CA-125 negative SKOV-3 tumors. Targeted nanobubbles also exhibited increased tumor retention and prolonged echogenicity compared to untargeted nanobubbles. Data suggest that ultrasound molecular imaging using CA-125 antibody-conjugated nanobubbles may contribute to improved diagnosis of EOC.

Keywords: Ca-125; Contrast enhanced ultrasound; Molecular imaging; Nanobubbles; Ovarian cancer; Targeted contrast agents.

MeSH terms

Animals
Antibodies, Immobilized / chemistry*
CA-125 Antigen / analysis*
Cell Line, Tumor
Contrast Media / chemistry*
Female
Humans
Mice, Inbred BALB C
Mice, Nude
Microbubbles*
Molecular Imaging / methods*
Ovarian Neoplasms / diagnostic imaging*
Ovary / diagnostic imaging*
Ultrasonography / methods

Substances

Antibodies, Immobilized
CA-125 Antigen
Contrast Media

Grants and funding

R01 CA136857/CA/NCI NIH HHS/United States