title: In vivo imaging of intraprostatic-specific gene transcription by PET.
abstract: Better intraprostatic cancer imaging techniques are needed to guide clinicians in prostate cancer treatment decisions. Because many genes are specifically overexpressed in cancer cells, one strategy to improve prostate cancer detection is to image intraprostatic cancer-specific transcriptional activity. Because of the obstacles of weak cancer- or tissue-specific promoter activity and bladder clearance of many PET tracers, intraprostatic PET of gene transcriptional activity has not been previously reported.
  
  
  METHODS
  The two-step transcriptional amplification (TSTA) system that amplifies the prostate-specific antigen promoter activity was used for PET imaging of the reporter gene herpes simplex virus type-1 sr39 thymidine kinase (HSV1-sr39tk). The TSTA-sr39tk system was injected directly into prostates or prostatic tumors as a replication-incompetent adenovirus (AdTSTA-sr39tk) and imaged using PET.
  
  
  RESULTS
  AdTSTA-sr39tk was able to image prostate-specific antigen promoter transcriptional activity by 9-(4-(18)F-fluoro-3-[hydroxymethyl]butyl)guanine PET, in both mouse and canine prostates in vivo. Ex vivo small-animal PET images, scintigraphic counts, and sr39tk expression analysis confirmed the specificity of the observed signal.
  
  
  CONCLUSIONS
  Here, by combining the TSTA-amplified signal with a protocol for tracer administration, we show that in vivo PET detection of transcriptional activity is possible in both mouse and immunocompetent canine prostates. These results suggest that imaging applications using transcription-based tumor-specific promoters should be pursued to better visualize cancer foci that escape detection by conventional biopsies.
authors.affiliation: Institute of Urologic Oncology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pouliot
authors.forename: Breanne D W
authors.initials: BD
authors.lastname: Karanikolas
authors.forename: Mai
authors.initials: M
authors.lastname: Johnson
authors.forename: Makoto
authors.initials: M
authors.lastname: Sato
authors.forename: Saul J
authors.initials: SJ
authors.lastname: Priceman
authors.forename: David
authors.initials: D
authors.lastname: Stout
authors.forename: Joanne
authors.initials: J
authors.lastname: Sohn
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Jean B
authors.initials: JB
authors.lastname: deKernion
authors.forename: Lily
authors.initials: L
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004285:Dogs; D005240:Feasibility Studies; D017930:Genes, Reporter / Q000235:genetics; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D007121:Immunocompetence / Q000235:genetics; D008297:Male; D051379:Mice; D009367:Neoplasm Staging; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic / Q000235:genetics; D011467:Prostate / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D013937:Thymidine Kinase; D017430:Prostate-Specific Antigen