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Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography

Cancer Gene Therapy volume 12, pages 329–339 (2005)Cite this article

Abstract

Molecular imaging of a suicide transgene's expression will aid the development of efficient and precise targeting strategies, and imaging for cancer cell viability may assess therapeutic efficacy. We used the PET reporter probe, 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)guanine ([18F]FHBG) to monitor the expression of a mutant Herpes Simplex Virus 1 thymidine kinase (HSV1-sr39tk) in C6 glioma tumors implanted subcutaneously in nude mice that were repetitively being treated with the pro-drug Ganciclovir (GCV). [18F]-Fluorodeoxyglucose ([18F]FDG), a metabolic tracer, was used to assess tumor cell viability and therapeutic efficacy. C6 glioma tumors stably expressing the HSV1-sr39tk gene (C6sr39) accumulated [18F]FHBG prior to GCV treatment. Significant declines in C6sr39 tumor volumes and [18F]FHBG and [18F]FDG accumulation were observed following 2 weeks of GCV treatment. However, 3 weeks after halting GCV treatment, the tumors re-grew and [18F]FDG accumulation increased significantly; in contrast, tumor [18F]FHBG concentrations remained at background levels. Therefore, [18F]FHBG can be used to detect tumors expressing HSV1-sr39tk, susceptible to regression in response to GCV exposure, and the effectiveness of GCV therapy in eradicating HSV1-sr39tk-expressing cells can be monitored by [18F]FHBG scanning. [18F]FHBG and [18F]FDG imaging data indicate that exposure of C6sr39 tumors to GCV causes the elimination of [18F]FHBG-accumulating C6sr39 cells and selects for re-growth of tumors unable to accumulate [18F]FHBG.

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Acknowledgements

We thank Ron Sumida, David Stout, Waldemar Ladno, and Judy Edwards for assistance with MicroPET imaging and the UCLA cyclotron crew for outstanding support in the synthesis of imaging tracers. This work was partially supported by funding from NIH Grants P50 CA86306, RO1 CA82214-01, and SAIRP R24 CA92865 DOE contract DE-FC03-87ER60615. This work was partially supported by funding from NIH Grants P50 CA86306, RO1 CA82214-01, and SAIRP R24 CA92865 DOE contract DE-FC03-87ER60615.

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Authors and Affiliations

  1. Department of Molecular & Medical Pharmacology, UCLA School of Medicine, Los Angeles, California, 90095-1770, USA

    Shahriar S Yaghoubi, Jorge R Barrio, Mohammad Namavari, Nagichettiar Satyamurthy, Michael E Phelps, Harvey R Herschman & Sanjiv S Gambhir

  2. The Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, California, 90095-1770, USA

    Shahriar S Yaghoubi, Michael E Phelps, Harvey R Herschman & Sanjiv S Gambhir

  3. Department of Radiology Bio-X program, Stanford University School of Medicine, USA

    Shahriar S Yaghoubi & Sanjiv S Gambhir

  4. The Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, California, 90095-1770, USA

    Jorge R Barrio, Mohammad Namavari, Nagichettiar Satyamurthy, Michael E Phelps & Sanjiv S Gambhir

  5. UCLA/DOE Laboratory of Structural Biology & Molecular Medicine, UCLA School of Medicine, Los Angeles, California, 90095-1770, USA

    Jorge R Barrio, Mohammad Namavari, Nagichettiar Satyamurthy, Michael E Phelps, Harvey R Herschman & Sanjiv S Gambhir

  6. Molecular Biology Institute, UCLA School of Medicine, Los Angeles, California, 90095-1770, USA

    Harvey R Herschman

  7. UCLA-Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California, 90095-1770, USA

    Harvey R Herschman & Sanjiv S Gambhir

  8. Department of Biomathematics, UCLA School of Medicine, Los Angeles, California, 90095-1770, USA

    Sanjiv S Gambhir

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  1. Shahriar S Yaghoubi
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Correspondence to Sanjiv S Gambhir.

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Yaghoubi, S., Barrio, J., Namavari, M. et al. Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography. Cancer Gene Ther 12, 329–339 (2005). https://doi.org/10.1038/sj.cgt.7700795

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