Evaluation of [18F]tetrafluoroborate as a Potential PET Imaging Agent in a Sodium Iodide Symporter-Transfected Cell Line A549 and Endogenous NIS-Expressing Cell Lines MKN45 and K1.

Mengda Niu,Chuanhuizi Tian,Jingjing Qin,Liang Wang,Zhiping Peng,Yujia He,Yanyan Chen,Pufeng Huang,Alexei Bogdanov

doi:10.1155/2022/2679260

Abstract

[18F]tetrafluoroborate (TFB) has been introduced as the 18F-labeled PET imaging probe for the human sodium iodide symporter (NIS). Noninvasive NIS imaging using [18F]TFB has received much interest in recent years for evaluating various NIS-expressing tumors. Cancers are a global concern with enormous implications; therefore, improving diagnostic methods for accurate detection of cancer is extremely important. Our aim was to investigate the PET imaging capabilities of [18F]TFB in NIS-transfected lung cell line A549 and endogenous NIS-expressing tumor cells, such as thyroid cancer K1 and gastric cancer MKN45, and broaden its application in the medical field. Western blot and flow cytometry were used to assess the NIS expression level. Radioactivity counts of [18F]TFB, in vitro, in the three tumor cells were substantially higher than those in the KI inhibition group in the uptake experiment. In vivo PET imaging clearly delineated the three tumors based on the specific accumulation of [18F]TFB in a mouse model. Ex vivo biodistribution investigation showed high [18F]TFB absorption in the tumor location, which was consistent with the PET imaging results. These results support the use of NIS-transfected lung cell line A549 and NIS-expressing tumor cells MKN45 and K1, to investigate probing capabilities of [18F]TFB. We also demonstrate, for the first time, the feasibility of [18F]TFB in diagnosing stomach cancer. In conclusion, this study illustrates the promising future of [18F]TFB for tumor diagnosis and NIS reporter imaging.

Highlights

The human sodium iodide symporter (NIS) is a plasma membrane protein that mediates the active transport of iodide (I-) into cells and is the basis for the clinical utilization of radioiodine [1–3]
The NIS overexpression lentiviral vector was mainly composed of NIS, Green fluorescence protein (GFP), and puromycin resistance genes (Figure 1(a))
After the 293T cells were transfected with NIS lentivirus, flow cytometric analysis (FCA) showed that 97.84% of the NIS-293T cells expressed NIS

Summary

Introduction

The human sodium iodide symporter (NIS) is a plasma membrane protein that mediates the active transport of iodide (I-) into cells and is the basis for the clinical utilization of radioiodine [1–3]. Other monovalent anions having ionic radii/-volumes similar to I-, such as pertechnetate (TcO4-), perchlorate (ClO4-), and tetrafluoroborate (TFB-), can be transported by NIS. They have been well established as NIS substrates [4, 5]. NIS has a restricted tissue expression, including the thyroid, salivary glands, and stomach, thereby enabling good imaging contrast [5–10]. There are no reports on the toxicity of ectopic NIS expression in nonthyroidal cells, and NIS is unrelated to the host immune response [11–13]. NIS is a promising imaging reporter gene for tumor-specific diagnosis and treatment

Objectives

Methods

Results

Conclusion