Summary                         

[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. The aim of this study 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 with nanoScan PET/CT 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. The feasibility of [18F]TFB in diagnosing stomach cancer is also demonstrated, for the first time. In conclusion, this study illustrates the promising future of [18F]TFB for tumor diagnosis and NIS reporter imaging.

Results from nanoScan PET/CT

MKN45, K1, NIS-A549, and A549 cells were used to establish a tumor model, in which cells stably expressed NIS. Female BALB/c nude mice, 4-6 weeks of age, were subcutaneously injected with 100 μL of MKN45 and K1 cells (5×10⁶) into the right armpit of each mouse and injected 100 μL of NIS-A549 and A549 cells (5×10⁶) into the right and left armpits of each mouse, respectively. Mice were also injected with the gastric cancer cell line MKN45 and thyroid cancer cell line K1. On the day of in vivo imaging, mice were intravenously injected with 200μL of [18F]TFB (1.85MBq) and were scanned using nanoScan PET/CT with static imaging after 60min pi.

Results show:

• normal [18F]TFB distribution in the control group (thyroid, salivary glands, stomach, kidney, and bladder). In addition, the [18F]NaF-PET image data of ordinary Kunming mice (b) revealed that the major signals were nearly entirely focused on the bone, demonstrated the successful synthesis of [18F]TFB.

• remarkable uptake of the radiotracer in the tumors and organs (thyroid, salivary glands, and stomach) endogenously expressing NIS in mice bearing both MKN45, K1 and A549 and NIS-A549 xenografts

The PET images demonstrated NIS specificity of [18F]TFB uptake in vivo by the following observations: (i) [18F]TFB showed robust uptake in NIS-positive tumors, but no significant tracer uptake was observed in NIS-negative tumors (Figure 7(b)); (ii) robust uptake of [18F]TFB was also observed in the thyroid, stomach, kidney, bladder, and NIS-positive tumors of the MKN45 and K1 xenograft mouse models, respectively (Figures 7(a) and 7(c)); (iii) there was no significant uptake in the bones, corroborating the results of negligible defluorination of [18F]TFB in mice.

Collectively, these results demonstrated the superior stability and good tumor-targeting properties of [18F]TFB.

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