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-beta-D-arabino-furanosyl-5-iodo-uracil (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.
authors.affiliation: Departments of Neurology and Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Surren A
authors.initials: SA
authors.lastname: Soghomonyan
authors.forename: Michael
authors.initials: M
authors.lastname: Doubrovin
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pike
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.forename: Martina
authors.initials: M
authors.lastname: Ittensohn
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Runyan
authors.forename: Julius
authors.initials: J
authors.lastname: Balatoni
authors.forename: Ronald
authors.initials: R
authors.lastname: Finn
authors.forename: Juri Gelovani
authors.initials: JG
authors.lastname: Tjuvajev
authors.forename: Ronald
authors.initials: R
authors.lastname: Blasberg
authors.forename: David
authors.initials: D
authors.lastname: Bermudes
mesh_terms: D000818:Animals; D001345:Autoradiography; D001428:Bacterial Vaccines; D002277:Carcinoma / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D017930:Genes, Reporter; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D012475:Salmonella / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014613:Vaccines, Attenuated
chemical_list: D001428:Bacterial Vaccines; C465023:VNP 20009; D014613:Vaccines, Attenuated; D013937:Thymidine Kinase