Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK. Academic Article uri icon

Overview

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.

publication date

  • January 1, 2005

Research

keywords

  • Genes, Reporter
  • Herpesvirus 1, Human
  • Positron-Emission Tomography
  • Salmonella
  • Thymidine Kinase

Identity

Scopus Document Identifier

  • 10844239971

Digital Object Identifier (DOI)

  • 10.1038/sj.cgt.7700779

PubMed ID

  • 15499377

Additional Document Info

volume

  • 12

issue

  • 1