18F-Tetrafluoroborate, a PET Probe for Imaging Sodium/Iodide Symporter Expression: Whole-Body Biodistribution, Safety, and Radiation Dosimetry in Thyroid Cancer Patients

Abstract

We report the safety, biodistribution, and internal radiation dosimetry, in humans with thyroid cancer, of ¹⁸F-tetrafluoroborate (¹⁸F-TFB), a novel PET radioligand for imaging the human sodium/iodide symporter (hNIS). Methods: Serial whole-body PET scans of 5 subjects with recently diagnosed thyroid cancer were acquired before surgery for up to 4 h after injection of 184 ± 15 MBq of ¹⁸F-TFB. Activity was determined in whole blood, plasma, and urine. Mean organ-absorbed doses and effective doses were calculated via quantitative image analysis and using OLINDA/EXM software. Results: Images showed a high uptake of ¹⁸F-TFB in known areas of high hNIS expression (thyroid, salivary glands, and stomach). Excretion was predominantly renal. No adverse effects in relation to safety of the radiopharmaceutical were observed. The effective dose was 0.0326 ± 0.0018 mSv/MBq. The critical tissues/organs receiving the highest mean sex-averaged absorbed doses were the thyroid (0.135 ± 0.079 mSv/MBq), stomach (0.069 ± 0.022 mSv/MBq), and salivary glands (parotids, 0.031 ± 0.011 mSv/MBq; submandibular, 0.061 ± 0.031 mSv/MBq). Other organs of interest were the bladder (0.102 ± 0.046 mSv/MBq) and kidneys (0.029 ± 0.009 mSv/MBq). Conclusion: Imaging using ¹⁸F-TFB imparts a radiation exposure similar in magnitude to many other ¹⁸F-labeled radiotracers. ¹⁸F-TFB shows a biodistribution similar to ^99mTc-pertechnetate, a known nonorganified hNIS tracer, and is pharmacologically and radiobiologically safe in humans. Phase 2 trials for ¹⁸F-TFB as an hNIS imaging agent are warranted.

Keywords: 18F-TFB; PET/CT; thyroid imaging.

Figure 1

Imaging scan schedule for the whole-body dynamic PET-CT study (not to scale). Dots above the scan positions show the timings of venous blood sampling and squares represent nominal urine sampling times.

Figure 2

Decay-corrected serial maximum-intensity projections showing the biodistribution of 18F-TFB over the course of the imaging study. Thyroid, salivary gland and stomach activities increase rapidly with time up to 30 minutes. Image captioned t = 0-9 min represents the first imaging frame.

Figure 3

Percentage of injected dose per gram of tissue (%ID/g) curves for selected organs, averaged over all 5 patients. Large standard deviations are evident in the hNIS expressing tissues and organs

Figure 4

Top - Mean decay-corrected blood and plasma curves averaged over all 5 patients. Bottom - mean blood cells to plasma distribution ratio, showing that equilibrium is reached after approximately 30 minutes. Error bars in both plots represent 1 standard deviation of the mean.