Androgen-independent molecular imaging vectors to detect castration-resistant and metastatic prostate cancer

Ziyue Karen Jiang, Makoto Sato, Liu H. Wei, Chinghai Kao, Lily Wu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Prostate-specific promoters are frequently employed in gene-mediated molecular imaging and therapeutic vectors to diagnose and treat castration-resistant prostate cancer (CRPC) that emerges from hormone ablation therapy. Many of the conventional prostate-specific promoters rely on the androgen axis to drive gene expression. However, considering the cancer heterogeneity and varying androgen receptor status, we herein evaluated the utility of prostate-specific enhancing sequence (PSES), an androgen-independent promoter in CRPC. The PSES is a fused enhancer derived from the prostate-specific antigen (PSA) and prostate-specific membrane antigen gene regulatory region. We augmented the activity of PSES by the two-step transcriptional amplification (TSTA) system to drive the expression of imaging reporter genes for either bioluminescent or positron emission tomography (PET) imaging. The engineered PSES-TSTA system exhibits greatly elevated transcriptional activity, androgen independency, and strong prostate specificity, verified in cell culture and preclinical animal experimentations. These advantageous features of PSES-TSTA elicit superior gene expression capability for CRPC in comparison with the androgen-dependent PSA promoter-driven system. In preclinical settings, we showed robust PET imaging capacity of PSES-TSTA in a castrated prostate xenograft model. Moreover, intravenous administrated PSES-TSTA bioluminescent vector correctly identified tibial bone marrow metastases in 9 of 9 animals, whereas NaF- and FDG-PET was unable to detect the lesions. Taken together, this study showed the promising utility of a potent, androgen-independent, and prostate cancer-specific expression system in directing gene-based molecular imaging in CRPC, even in the context of androgen deprivation therapy.

Original languageEnglish
Pages (from-to)6250-6260
Number of pages11
JournalCancer Research
Volume71
Issue number19
DOIs
StatePublished - Oct 1 2011

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Molecular Imaging
Castration
Androgens
Prostate
Prostatic Neoplasms
Positron-Emission Tomography
Prostate-Specific Antigen
Genes
Gene Expression
Nucleic Acid Regulatory Sequences
Androgen Receptors
Reporter Genes
Heterografts
Therapeutics
Cell Culture Techniques
Bone Marrow
Hormones
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Androgen-independent molecular imaging vectors to detect castration-resistant and metastatic prostate cancer. / Jiang, Ziyue Karen; Sato, Makoto; Wei, Liu H.; Kao, Chinghai; Wu, Lily.

In: Cancer Research, Vol. 71, No. 19, 01.10.2011, p. 6250-6260.

Research output: Contribution to journalArticle

Jiang, Ziyue Karen ; Sato, Makoto ; Wei, Liu H. ; Kao, Chinghai ; Wu, Lily. / Androgen-independent molecular imaging vectors to detect castration-resistant and metastatic prostate cancer. In: Cancer Research. 2011 ; Vol. 71, No. 19. pp. 6250-6260.
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