Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK Journal Article
| Authors: | Soghomonyan, S. A.; Doubrovin, M.; Pike, J.; Luo, X.; Ittensohn, M.; Runyan, J. D.; Balatoni, J.; Finn, R.; Tjuvajev, J. G.; Blasberg, R.; Bermudes, D. |
| Article Title: | Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK |
| Abstract: | In order to noninvasively detect Salmonella delivery vectors within tumors, we used a genetically modified Salmonella, VNP20009, that expresses the herpes simplex thymidine kinase (HSV1-tk) reporter gene. VNP20009-TK were able to selectively localize within murine tumor models and to effectively sequester a radiolabeled nucleoside analogue, 2′-fluoro-1-β-D-arabino-furanosyl- 5-iodouracil (FIAU). A quantitative relationship between the level of radioactivity accumulated and the number of bacteria in tumor and different tissues was demonstrated. The in vivo accumulation of [ 14C]FIAU measured in tissue sample homogenates and sections were related to Salmonella number and to immunohistochemical bacterial staining, respectively. Quantitative autoradiography (QAR) revealed the relative intensity of [ 14C]FIAU accumulation in a tumor cross-section, demonstrating that the peripheral region of the tumor was significantly less active than internal regions. [ 124I]FIAU positron emission tomography (PET) and subsequent tissue radioactivity and bacterial concentration measurements were compared. A log-log relationship was found, and the PET images could identify multiple tumor sites. The ability to noninvasively detect Salmonella vectors by PET imaging has the potential to be conducted in a clinical setting, and could aid in development of these vectors by demonstrating the efficiency and duration of targeting as well as indicating the locations of tumors. |
| Keywords: | immunohistochemistry; nonhuman; positron emission tomography; animal cell; mouse; animals; mice; animal tissue; tumor localization; melanoma; skin neoplasms; animal experiment; animal model; colonic neoplasms; in vivo study; molecular imaging; bacteria (microorganisms); mice, inbred c57bl; gene vector; animalia; genetic vectors; dna modification; tumor targeting; drug accumulation; isotope labeling; radioactivity; positron-emission tomography; carcinoma; murinae; simplexvirus; reporter gene; fialuridine; thymidine kinase; genes, reporter; herpesvirus 1, human; disease models, animal; colon carcinoma; herpes simplex virus 1; autoradiography; sampling; nonviral gene delivery system; nonviral gene therapy; salmonella; human herpesvirus 1; bacterial count; vaccines, attenuated; gram staining; gene expression system; bacterial therapy; tapet; vnp20009-tk |
| Journal Title: | Cancer Gene Therapy |
| Volume: | 12 |
| Issue: | 1 |
| ISSN: | 0929-1903 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2005-01-01 |
| Start Page: | 101 |
| End Page: | 108 |
| Language: | English |
| DOI: | 10.1038/sj.cgt.7700779 |
| PUBMED: | 15499377 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 39" - "Export Date: 24 October 2012" - "CODEN: CGTHE" - "Source: Scopus" |
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