EVALUATION OF SALMONELLA-BASED SUICIDE GENE TRANSFER IN A RODENT TUMOR MODEL USING IN VIVO 19F MR SPECTROSCOPY.
Van Hecke P, Landuyt W, Dresselaers T, Theys J, Dubois L, Lambin P
Salmonella typhimurium recombinant for cytosine deaminase (TAPET-CD) is a non-pathogenic bacterial-mediated vector system that, in combination with systemic delivery of 5-Fluorocytosine (5-FC), can result in anti-tumor effects (1-4). We already demonstrated that engineered Salmonella persist in tumors for extensive time periods without the need for repeated administration. Importantly, we also showed the feasibility of 19F-MR Spectroscopy (19F-MRS) to monitor in vivo the intra-tumoral conversion from 5-FC to the cytostatic 5-fluorouracil (5-FU) (5). Here we report on a longitudinal 19F MRS study of this TAPET-CD/5-FC therapy in mice xenografted with the human colorectal carcinoma HCT116. Initial results in this model indicate that the 5-FU formation, as observed with in vivo 19F MRS, 10 days after the first 5-FC administration correlates with the response of the tumor to the therapy (based on tumor growth over several weeks).