RT Journal Article
SR Electronic
T1 In Vivo Imaging of Intraprostatic-Specific Gene Transcription by PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 784
OP 791
DO 10.2967/jnumed.110.084582
VO 52
IS 5
A1 Pouliot, Frédéric
A1 Karanikolas, Breanne D.W.
A1 Johnson, Mai
A1 Sato, Makoto
A1 Priceman, Saul J.
A1 Stout, David
A1 Sohn, Joanne
A1 Satyamurthy, Nagichettiar
A1 deKernion, Jean B.
A1 Wu, Lily
YR 2011
UL http://jnm.snmjournals.org/content/52/5/784.abstract
AB 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-(4-18F-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. Conclusion: 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.