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In Vivo Imaging of Thyroid Cancer with Tc-TR1401 and Tc-TR1402: A Comparison Study in Dogs. | LitMetric

In Vivo Imaging of Thyroid Cancer with Tc-TR1401 and Tc-TR1402: A Comparison Study in Dogs.

J Clin Med

Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, "Sapienza" University of Rome, 00161 Rome, Italy.

Published: April 2021

AI Article Synopsis

Article Abstract

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 Tc-TR1401 SPECT/CT, Tc-TR1402 SPECT/CT, and [F]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 Tc-TR1401 and 0.5 nM for Tc-TR1402 compared with Tc-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. Tc-TR1402 provided higher T/B than Tc-TR1401 and [F]FDG (12.9 ± 1.3, 10.2 ± 0.7, and 3.8 ± 0.6, respectively; all < 0.001). Given these results, Tc-TR1402 appears to be a useful tool for in vivo imaging of thyroid cancer.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123688PMC
http://dx.doi.org/10.3390/jcm10091878DOI Listing

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