AEG-1 promoter-mediated imaging of prostate cancer

Cancer Res. 2014 Oct 15;74(20):5772-81. doi: 10.1158/0008-5472.CAN-14-0018. Epub 2014 Aug 21.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / diagnostic imaging*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary
  • Cell Adhesion Molecules / genetics*
  • Cell Line, Tumor
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Luciferases, Firefly / biosynthesis
  • Luciferases, Firefly / genetics
  • Male
  • Membrane Proteins
  • Mice, Inbred NOD
  • Mice, SCID
  • Molecular Diagnostic Techniques*
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • RNA-Binding Proteins
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Transcriptional Activation

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Luciferases, Firefly