title: AEG-1 promoter-mediated imaging of prostate cancer.
abstract: We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through a systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single-photon emission computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for noninvasive clinical imaging. Furthermore, the approach compares favorably with accepted and emerging clinical standards, including PET with [(18)F]fluorodeoxyglucose and [(18)F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Akrita
authors.initials: A
authors.lastname: Bhatnagar
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gabrielson
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Polina
authors.initials: P
authors.lastname: Sysa
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Il
authors.initials: I
authors.lastname: Minn
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Green
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Brian
authors.initials: B
authors.lastname: Simmons
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gabrielson
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Siddik
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia. VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia. VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland. mpomper@jhmi.edu.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D025202:Molecular Diagnostic Techniques; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D016601:RNA-Binding Proteins; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015533:Transcriptional Activation
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D049409:Luciferases, Firefly