In Vivo Imaging of Thyroid Cancer with 99mTc-TR1401 and 99mTc-TR1402: A Comparison Study in Dogs.
Filippo GalliMichela VaraniChiara LauriGiuseppe CampagnaLajos BaloghBruce D WeintraubMariusz W SzkudlinskiArmando BartolazziIsabella ManniGiulia PiaggioAlberto SignorePublished in: Journal of clinical medicine (2021)
Differentiated thyroid cancer (DTC) cells may lose NIS expression and iodine uptake, but usually express TSH receptors (TSHR). Therefore, the aim of our study was to compare two radiolabeled superagonist TSH analogues for DTC imaging. These analogues (namely TR1401 and TR1402) have a higher TSHR binding affinity than recombinant human TSH (Thyrogen®). Radiolabeling was performed with technetium-99m using an indirect method via HYNIC conjugation and was followed by in vitro quality controls and binding assay on TSHR-positive cell lines (ML-1). An in vitro binding assay was also performed and compared with radiolabeled human recombinant TSH. In vivo imaging was performed in four dogs with spontaneous follicular thyroid carcinoma with solid poorly differentiated areas with 99mTc-TR1401 SPECT/CT, 99mTc-TR1402 SPECT/CT, and [18F]FDG PET/CT on different days within 2 weeks. TR1401 and TR1402 were labeled with high specific activity (8.3 ± 1.2 MBq/µg) and retention of their biological activity and structural integrity. Both agonists were able to efficiently bind TSHR receptors expressed by cell lines with dissociation constants (Kd) of 2.7 nM for 99mTc-TR1401 and 0.5 nM for 99mTc-TR1402 compared with 99mTc-Thyrogen (Kd = 8.4 nM). In tumor-targeting experiments, a focal uptake was observed in dogs with spontaneous intraglandular thyroid carcinoma, in which TSHR expression was confirmed by immunohistochemistry. 99mTc-TR1402 provided higher T/B than 99mTc-TR1401 and [18F]FDG (12.9 ± 1.3, 10.2 ± 0.7, and 3.8 ± 0.6, respectively; all p < 0.001). Given these results, 99mTc-TR1402 appears to be a useful tool for in vivo imaging of thyroid cancer.
Keyphrases
- high resolution
- poor prognosis
- pet ct
- computed tomography
- photodynamic therapy
- high throughput
- endothelial cells
- binding protein
- recombinant human
- dual energy
- magnetic resonance imaging
- cancer therapy
- magnetic resonance
- oxidative stress
- image quality
- single cell
- mass spectrometry
- endoplasmic reticulum stress
- molecular docking
- cell proliferation
- transcription factor
- cell death
- contrast enhanced
- cell cycle arrest
- preterm birth