OncoTargets and Therapy (Nov 2020)
18F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model
Abstract
Xiaofeng Li,1– 3,* Guotao Yin,1– 3,* Wei Ji,2– 4,* Jianjing Liu,1– 3 Yufan Zhang,1– 3 Jian Wang,1– 3 Xiang Zhu,1– 3 Lei Zhu,1– 3 Dong Dai,1– 3 Wenchao Ma,1– 3 Wengui Xu1– 3 1Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 3Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 4Public Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wengui XuDepartment of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huan-Hu-Xi Road, Ti-Yuan-Bei, He Xi District, Tianjin 300060, People’s Republic of ChinaTel +86 22 23340123Fax +86-22-23359337Email [email protected]: 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.Keywords: breast cancer, CIK immunotherapy, HSV1-TK, reporter gene, 18F-FHBG PET-CT
