1. ¹Departments of Neurology and Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York 10021, USA
2. ²Vion Pharmaceuticals, Inc., 4 Science Park, New Haven, Connecticut 06511, USA

Correspondence: Dr Ronald G Blasberg, MD, Departments of Neurology and Radiology (Box 52), Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. E-mail: blasberg@neurol.mskcc.org

^aCurrent address: Alexion Pharmaceuticals, Inc., 352 Knotter Drive, Cheshire, CT 06410, USA.

^bCurrent address: RibX Pharmaceuticals, Inc., 300 George St, Suite 301, New Haven, CT 06511, USA.

^cCurrent address: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877-0368, USA.

^dCurrent address: Dept. of Experimental Diagnostic Imaging, M. D. Anderson Cancer Center, Unit 057, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Received 10 February 2004; Published online 22 October 2004.

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--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.