Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach
Cancer gene therapy based on tissue-restricted expression of cytotoxic gene should achieve superior therapeutic index over an unrestricted method. This study compared the therapeutic effects of a highly augmented, prostate-specific gene expression method to a strong constitutive promoter-driven appr...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2005-10-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2005.05154 |
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| _version_ | 1841564492795740160 |
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| author | Mai Johnson Makoto Sato Jeremy Burton Sanjiv S. Gambhir Michael Carey Lily Wu |
| author_facet | Mai Johnson Makoto Sato Jeremy Burton Sanjiv S. Gambhir Michael Carey Lily Wu |
| author_sort | Mai Johnson |
| collection | DOAJ |
| description | Cancer gene therapy based on tissue-restricted expression of cytotoxic gene should achieve superior therapeutic index over an unrestricted method. This study compared the therapeutic effects of a highly augmented, prostate-specific gene expression method to a strong constitutive promoter-driven approach. Molecular imaging was coupled to gene therapy to ascertain real-time therapeutic activity. The imaging reporter gene (luciferase) and the cytotoxic gene (herpes simplex thymidine kinase) were delivered by adenoviral vectors injected directly into human prostate tumors grafted in SCID mice. Serial bioluminescence imaging, positron emission tomography, and computed tomography revealed restriction of gene expression to the tumors when prostate-specific vector was employed. In contrast, administration of constitutive active vector resulted in strong signals in the liver. Liver serology, tissue histology, and frail condition of animals confirmed liver toxicity suffered by the constitutive active cohorts, whereas the prostate-targeted group was unaffected. The extent of tumor killing was analyzed by apoptotic staining and human prostate marker (prostate-specific antigen). Overall, the augmented prostate-specific expression system was superior to the constitutive approach in safeguarding against systemic toxicity, while achieving effective tumor killing. Integrating noninvasive imaging into cytotoxic gene therapy will provide a useful strategy to monitor gene expression and therapeutic efficacy in future clinical protocols. |
| format | Article |
| id | doaj-art-c9be0301d0834bde9b888f55a0dfb2e2 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2005-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-c9be0301d0834bde9b888f55a0dfb2e22025-01-02T22:41:16ZengSAGE PublishingMolecular Imaging1536-01212005-10-01410.2310/7290.2005.0515410.2310_7290.2005.05154Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting ApproachMai Johnson0Makoto Sato1Jeremy Burton2Sanjiv S. Gambhir3Michael Carey4Lily Wu5University of California Los AngelesUniversity of California Los AngelesUniversity of California Los AngelesStanford University, USAUniversity of California Los AngelesUniversity of California Los AngelesCancer gene therapy based on tissue-restricted expression of cytotoxic gene should achieve superior therapeutic index over an unrestricted method. This study compared the therapeutic effects of a highly augmented, prostate-specific gene expression method to a strong constitutive promoter-driven approach. Molecular imaging was coupled to gene therapy to ascertain real-time therapeutic activity. The imaging reporter gene (luciferase) and the cytotoxic gene (herpes simplex thymidine kinase) were delivered by adenoviral vectors injected directly into human prostate tumors grafted in SCID mice. Serial bioluminescence imaging, positron emission tomography, and computed tomography revealed restriction of gene expression to the tumors when prostate-specific vector was employed. In contrast, administration of constitutive active vector resulted in strong signals in the liver. Liver serology, tissue histology, and frail condition of animals confirmed liver toxicity suffered by the constitutive active cohorts, whereas the prostate-targeted group was unaffected. The extent of tumor killing was analyzed by apoptotic staining and human prostate marker (prostate-specific antigen). Overall, the augmented prostate-specific expression system was superior to the constitutive approach in safeguarding against systemic toxicity, while achieving effective tumor killing. Integrating noninvasive imaging into cytotoxic gene therapy will provide a useful strategy to monitor gene expression and therapeutic efficacy in future clinical protocols.https://doi.org/10.2310/7290.2005.05154 |
| spellingShingle | Mai Johnson Makoto Sato Jeremy Burton Sanjiv S. Gambhir Michael Carey Lily Wu Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach Molecular Imaging |
| title | Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach |
| title_full | Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach |
| title_fullStr | Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach |
| title_full_unstemmed | Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach |
| title_short | Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach |
| title_sort | micro pet ct monitoring of herpes thymidine kinase suicide gene therapy in a prostate cancer xenograft the advantage of a cell specific transcriptional targeting approach |
| url | https://doi.org/10.2310/7290.2005.05154 |
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