Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK.
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.
Soghomonyan
Surren A
SA
Departments of Neurology and Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Doubrovin
Michael
M
Pike
Jeremy
J
Luo
Xiang
X
Ittensohn
Martina
M
Runyan
Jacob D
JD
Balatoni
Julius
J
Finn
Ronald
R
Tjuvajev
Juri Gelovani
JG
Blasberg
Ronald
R
Bermudes
David
D
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
D001428:Bacterial Vaccines; C465023:VNP 20009; D014613:Vaccines, Attenuated; D013937:Thymidine Kinase