MP61-13 DEVELOPMENT OF A MOLECULAR IMAGING SYSTEM BASED ON THE TRANSCRIPTIONAL ACTIVITY OF THE DD3/PCA3 NON-CODING RNA FOR IMAGING SPECIFICALLY THE PROSTATE CANCER CELLS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2015MP61-13 DEVELOPMENT OF A MOLECULAR IMAGING SYSTEM BASED ON THE TRANSCRIPTIONAL ACTIVITY OF THE DD3/PCA3 NON-CODING RNA FOR IMAGING SPECIFICALLY THE PROSTATE CANCER CELLS Pallavi Jain, Bertrand Neveu, Yves Fradet, and Frederic Pouliot Pallavi JainPallavi Jain More articles by this author , Bertrand NeveuBertrand Neveu More articles by this author , Yves FradetYves Fradet More articles by this author , and Frederic PouliotFrederic Pouliot More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2194AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Molecular imaging plays an important role in oncology for staging of tumors. Unfortunately, the specificity and sensitivity of current techniques remains low. This study aims to improve the existing imaging system based on transcriptional activation, named as “Two -Step- Transcriptional Amplification (TSTA) system”, with the goal to precisely image in vivo prostate cancer cells (PCa) by Positron Emission Tomography (PET). We have studied the potential of DD3/PCA3 promoter, a gene specifically expressed in PCa, to achieve this goal. METHODS Various adenovirus constructs incorporating the DD3 promoter, the TSTA system and the Firefly luciferase reporter gene were generated and their specificity for PCa cells was tested in transient infection. By molecular engineering, we have improved the TSTA system and generated the 3STA. The luciferase activities of DD3-TSTA, DD3-3STA and PSA-TSTA (Prostate Specific Antigen) were compared in vivo by bioluminescence in xenograft mouse models. Ex vivo prostate biopsy from RP (radical prostatectomy) specimen were exposed to DD3-3STA and luciferase expression was evaluated using bioluminescence and Immunohistochemistry. RESULTS The DD3 promoter activity is both specific to prostate and cancer cells. When DD3 promoter is incorporated in the amplification systems TSTA and 3STA, it is specific to PCa cells and its activity is amplified more than 300 and 600 times, respectively, when compared to the activity of the DD3 promoter alone. Moreover, activity of DD3-TSTA and DD3-3STA is androgen-independent. In vivo, DD3-3STA activity is comparable to that obtained with the PSA-TSTA whose activity can be imaged by PET. DD3-3STA could detect primary prostate cancer cells ex vivo in prostate biopsy obtained from RP specimen (Figure 1). CONCLUSIONS The new system DD3-3STA allows specific and sensitive imaging of PCa cells. The new amplification system 3STA allows the DD3 promoter to produce reporter signal high enough to be detected by PET, a technology available in the clinic. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e751 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pallavi Jain More articles by this author Bertrand Neveu More articles by this author Yves Fradet More articles by this author Frederic Pouliot More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...