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Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging

Nature Medicine volume 8, pages 891–896 (2002)Cite this article

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.

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Figure 1: Adenoviral vector-mediated luciferase gene delivery and expression in the liver after systemic administration.
Figure 2: Kinetics of transgene expression in living mice after intratumoral injection.
Figure 3: Detailed histological analysis of spinal metastatic lesions.
Figure 4: Optical CCD detection and histological analysis of lung metastases.
Figure 5: Androgen-regulated gene expression in prostate cancer models.

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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.).

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Authors and Affiliations

  1. Department of Urology, UCLA, Los Angeles, 90095, California, USA

    Jason Y. Adams, Mai Johnson, Makoto Sato & Lily Wu

  2. Crump Institute for Molecular Imaging & Department of Molecular & Medical Pharmacology, UCLA, Los Angeles, 90095, California, USA

    Frank Berger & Sanjiv S. Gambhir

  3. Department of Biological Chemistry, David Geffen School of Medicine at UCLA, UCLA, Los Angeles, 90095, California, USA

    Michael Carey

  4. Department of Molecular Cell and Developmental Biology, College of Letters & Science, UCLA, Los Angeles, 90095, California, USA

    M. Luisa Iruela-Arispe

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  1. Jason Y. Adams
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Correspondence to Lily Wu.

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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

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