18 F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model

Background To further improve the efficiency of adoptively transferred cytokine-induced killer (CIK) cell immunotherapy in breast cancer (BC), a reliable imaging method is required to visualize and monitor these transferred cells in vivo. Methods Herpes simplex virus 1-thymidine kinase (HSV1-TK) and 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)guanine (18F-FHBG) were used as a pair of reporter gene/reporter probe for positron emission tomography (PET) imaging in this study. Following the establishment of subcutaneous BC xenograft-bearing nude mice models, induced human CIK cells expressing reporter gene HSV1-TK through lentiviral transduction were intravenously injected to nude mice. γ-radioimmunoassay was used to determine the specific uptake of 18F-FHBG by these genetically engineered CIK cells expressing HSV1-TK in vitro, and 18F-FHBG micro positron emission tomography-computed tomography (PET-CT) imaging was performed to visualize these adoptively transferred CIK cells in tumor-bearing nude mice. Results Specific uptake of 18F-FHBG by CIK cells expressing HSV1-TK was clearly observed in vitro. Consistently, the localization of adoptively transferred CIK cells in tumor target could be effectively visualized by 18F-FHBG micro PET-CT reporter gene imaging. Conclusion PET-CT reporter gene imaging using 18F-FHBG as a reporter probe enables the visualization and monitoring of adoptively transferred CIK cells in vivo.