Abstract
Non-invasive imaging and transcriptional targeting can improve the safety of therapeutic approaches in cancer. Here we demonstrate the ability to identify metastases in a human-prostate cancer model, employing a prostate-specific adenovirus vector (AdPSE-BC-luc) and a charge-coupled device-imaging system. AdPSE-BC-luc, which expresses firefly luciferase from an enhanced prostate-specific antigen promoter, restricted expression in the liver but produced robust signals in prostate tumors. In fact, expression was higher in advanced, androgen-independent tumors than in androgen-dependent lesions. Repetitive imaging over a three-week period after AdPSE-BC-luc injection into tumor-bearing mice revealed that the virus could locate and illuminate metastases in the lung and spine. Systemic injection of low doses of AdPSE-BC-luc illuminated lung metastasis. These results demonstrate the potential use of a non-invasive imaging modality in therapeutic and diagnostic strategies to manage prostate cancer.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Nash, A.F. & Melezinek, I. The role of prostate specific antigen measurement in the detection and management of prostate cancer. Endocr. Relat. Cancer 7, 37–51 (2000).
Rini, B.I. & Small, E.J. An update on prostate cancer. Curr. Opin. Oncol. 13, 204–211 (2001).
Bloomfield, D.J. et al. Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points. J. Clin. Oncol. 16, 2272–2279 (1998).
Harrington, K.J., Spitzweg, C., Bateman, A.R., Morris, J.C. & Vile, R.G. Gene therapy for prostate cancer: Current status and future prospects. J. Urol. 166, 1220–1233 (2001).
Wu, L. et al. Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors. Gene Ther. 8, 1416–1426 (2001).
Klein, K.A. et al. Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice. Nature Med. 3, 402–408 (1997).
Craft, N. et al. Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res. 59, 5030–5036 (1999).
Rehemtulla, A. et al. Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. Neoplasia 2, 491–495 (2000).
Wu, J.C., Sundaresan, G., Iyer, M. & Gambhir, S.S. Noninvasive optical imaging of firefly luciferase reporter gene expression in skeletal muscles of living mice. Mol. Ther. 4, 297–306 (2001).
Tao, N. et al. Sequestration of adenoviral vector by Kupffer cells leads to a nonlinear dose response of transduction in liver. Mol. Ther. 3, 28–35 (2001).
Yang, Y. et al. Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc. Natl. Acad. Sci. USA 91, 4407–4411 (1994).
Waller, A.S., Sharrard, R.M., Berthon, P. & Maitland, N.J. Androgen receptor localisation and turnover in human prostate epithelium treated with the antiandrogen, casodex. J. Mol. Endocrinol. 24, 339–351 (2000).
Zhao, X.Y. et al. Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nature Med. 6, 703–706 (2000).
Linja, M.J. et al. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 61, 3550–3555 (2001).
Craft, N., Shostak, Y., Carey, M. & Sawyers, C.L. A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nature Med. 5, 280–285 (1999).
Gregory, C.W. et al. A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer Res. 61, 4315–4319 (2001).
Zhang, L. et al. Molecular engineering of a two-step transcription amplification (TSTA) system for transgene delivery in prostate cancer. Mol. Ther. 5, 223–232 (2002).
The Development of Human Gene Therapy. (ed. Freidmann, T.) (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1999).
Yaghoubi, S.S. et al. Direct correlation between positron emission tomographic images of two reporter genes delivered by two distinct adenoviral vectors. Gene Ther. 8, 1072–1080 (2001).
Leav, I. et al. Comparative studies of the estrogen receptors β and α and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma. Am. J. Pathol. 159, 79–92 (2001).
Acknowledgements
We thank A. Berk, U. Banerjee, H. Herschman, L. Rome, C. Sawyers, R. Reiter and J. Said for helpful advice and critical review of manuscript; Joseph Wu, Tina Yu, Joyce Yamashiro, Evelyn Kondo and Chris Tran for technical assistance; and W. Aft and D. Nusinow for assistance in the preparation of this manuscript. This work was initiated with seed funding from the California Cancer Research Coordinating Committee, the Carolan Foundation of UCLA and the California Cancer Research Program. L.W. is a member of the Jonsson Comprehensive Cancer Center and the recipient of a STOP Cancer research career development award. Cost of imaging was supported by NIH P50 CA86306 (S.S.G.), R0-1 CA82214 (S.S.G.), SAIRP R24 CA92865 (S.S.G.), Department of Energy Contract DE-FC03-87ER60615 (S.S.G.) and CaPCURE (S.S.G., M.C.).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Adams, J., Johnson, M., Sato, M. et al. Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging. Nat Med 8, 891–896 (2002). https://doi.org/10.1038/nm743
Published:
Issue Date:
DOI: https://doi.org/10.1038/nm743
This article is cited by
-
Biodistribution and immunity of adenovirus 5/35 and modified vaccinia Ankara vector vaccines against human immunodeficiency virus 1 clade C
Gene Therapy (2022)
-
A novel approach for assessment of prostate cancer aggressiveness using survivin-driven tumour-activatable minicircles
Gene Therapy (2019)
-
A Molecular Imaging System Based on Both Transcriptional and Genomic Amplification to Detect Prostate Cancer Cells In Vivo
Molecular Therapy (2013)
-
Multifunctional in vivo vascular imaging using near-infrared II fluorescence
Nature Medicine (2012)
-
Lung fluorescence imaging to evaluate tumor metastasis induced by AQP5 expression in murine model
Medical Oncology (2012)