title: Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer.
abstract: OBJECTIVE
  Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using64Cu-labeled pertuzumab for immunoPET imaging.
  
  
  METHODS
  HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed for non-invasive in vivo evaluation of HER2 expression. Additionally, orthotopic models were employed to further validate the imaging capability of64Cu-NOTA-pertuzumab.
  
  
  RESULTS
  HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression.64Cu-NOTA-pertuzumab showed high specificity for HER2 (Ka= 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3%ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively (n = 3). In orthotopic models, PET imaging with64Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-expressing ovarian cancer.
  
  
  CONCLUSIONS
  64Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification.
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China.|Department of Radiology, University of Wisconsin - Madison, Room 7137, 1111 Highland Ave, Madison, WI, 53705-2275, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Radiology, University of Wisconsin - Madison, Room 7137, 1111 Highland Ave, Madison, WI, 53705-2275, USA.|Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Hyung-Jun
authors.initials: HJ
authors.lastname: Im
authors.affiliation: Department of Radiology, University of Wisconsin - Madison, Room 7137, 1111 Highland Ave, Madison, WI, 53705-2275, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA.
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: England
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Ehlerding
authors.affiliation: Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.affiliation: Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Radiology, University of Wisconsin - Madison, Room 7137, 1111 Highland Ave, Madison, WI, 53705-2275, USA.
authors.forename: Steve Y
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China. peng.huang@szu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Radiology, University of Wisconsin - Madison, Room 7137, 1111 Highland Ave, Madison, WI, 53705-2275, USA. wcai@uwhealth.org.|Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA. wcai@uwhealth.org.|University of Wisconsin Carbone Cancer Center, Madison, WI, 53705, USA. wcai@uwhealth.org.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003301:Copper Radioisotopes; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011874:Radiometry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D018719:Erb-b2 Receptor Tyrosine Kinases; C000615411:Copper-64; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: Human epidermal growth factor receptor 2 (HER2); Molecular imaging; Ovarian cancer; Pertuzumab; Positron emission tomography (PET)