title: Targeted Contrast Agent Specific to an Oncoprotein in Tumor Microenvironment with the Potential for Detection and Risk Stratification of Prostate Cancer with MRI.
abstract: Accurate detection and risk stratification are paramount to the clinical management of prostate cancer. Current diagnostic methods, including prostate specific antigen (PSA) screening, are unable to differentiate high-risk tumors from low-risk tumors, resulting in overdiagnosis and overtreatment. A peptide targeted contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein in tumor microenvironment, EDB-FN, was synthesized for noninvasive detection and characterization of aggressive prostate cancer. EDB-FN, one of the subtypes of oncofetal fibronectin, is involved in tumor epithelial-to-mesenchymal transition (EMT), which is implicated in drug resistance and metastasis. The EDB-FN mRNA level in the metastatic PC3 cells was at least three times higher than that in non-metastatic LNCaP cells. In tumors, EDB-FN protein was highly expressed in PC3 tumor xenografts, but not in LNCaP tumors, as revealed by Western blot analysis. ZD2-Gd(HP-DO3A) produced over two times higher contrast-to-noise ratio in the PC3 tumors than in the LNCaP tumors in contrast-enhanced MRI during 30 min after injection. ZD2-Gd(HP-DO3A) possessed high chelate stability against transmetalation and minimal tissue accumulation. Our results demonstrate that molecular MRI of EDB-FN with ZD2-Gd(HP-DO3A) can potentially be used for noninvasive detection and risk stratification of human prostate cancer. Incorporation of this targeted contrast agent in the existing clinical contrast enhanced MRI procedures has the potential to improve diagnostic accuracy of prostate cancer.
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Han
authors.affiliation: Molecular Theranostics, LLC , Beachwood, Ohio 44122, United States.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Roelle
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Zhuxian
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Rob
authors.initials: R
authors.lastname: Sabatelle
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Aidan
authors.initials: A
authors.lastname: DeSanto
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Cristina
authors.initials: C
authors.lastname: Magi-Galluzzi
authors.affiliation: Case Center for Biomolecular Engineering, Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Zheng-Rong
authors.identifier: 0000-0001-8185-9519
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D045744:Cell Line, Tumor; D003287:Contrast Media / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D015513:Oncogene Proteins / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D018570:Risk Assessment; D059016:Tumor Microenvironment
chemical_list: D003287:Contrast Media; D015513:Oncogene Proteins