18F-FHBG micro PET-CT reporter gene imaging of adoptive CIK cell transfer immunotherapy in breast cancer

1065 Background: To further improve the efficiency of adoptively transferred CIK cell immunotherapy in breast cancer, a reliable imaging method is required to visualize and monitor these transferred cells in vivo. Methods: PET reporter gene herpes simplex virus 1- thymidine kinase (HSV1-TK) was cloned into pLVX5-GFP lentiviral vector. Human CIK cells were induced and expanded in vitro to be lentivirally transduced to express reporter gene HSV1-TK. Subsequently, these genetically engineered CIK cells were tail intravenously injected to established nude mice models bearing subcutaneous breast cancer xenografts. After radiosynthesis of 9-4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine (18F-FHBG) as a specific reporter probe for reporter gene HSV1-TK, γ-radioimmunoassay was used to determine the specific uptake of 18F-FHBG by cells expressing HSV1-TK in vitro. 18F-FHBG micro PET-CT reporter gene imaging was performed to visualize these adoptively transferred CIK cells in tumor-bearing nude mice. Results: Specific uptake of 18F-FHBG was obviously observed in cells expressing HSV1-TK in vitro. Consistently, an accumulation of 18F-FHBG was shown in breast cancer xenografts in vivo, and the maximal standard uptake values (SUVmax) was significantly higher in xenografts expressing HSV1-TK than that in control xenografts without HSV1-TK expression. The localization of adoptively transferred CIK cells in tumor target could be effectively visualized by 18F-FHBG micro PET-CT reporter gene imaging. Conclusions: PET-CT reporter gene imaging using 18F-FHBG as reporter probe enable the visualization and monitoring of adoptively transferred CIK cells in vivo.