Thyroid-Stimulating Hormone Receptor (TSHR) as a Target for Imaging Differentiated Thyroid Cancer

Thyroid cancer is diagnosed in half a million people annually. Differentiated thyroid cancers (DTCs) make up 95% of these diagnoses. While clinical guidelines recommend surgical resection followed by radioactive iodine (RAI) ablation, loss of sodium-iodine symporter (NIS) expression causes up to 20%...

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Published in:Surgery 2024-01, Vol.175 (1), p.199-206
Main Authors: Gimblet, Grayson R., Whitt, Jason, Houson, Hailey A., Lin, Diana, Guenter, Rachael, Rao, Tejeshwar C., Wang, Dezhi, Ness, John, Gonzalez, Manuel Lora, Murphy, Madisen S., Gillis, Andrea, Chen, Herbert, Copland, John A., Kenderian, Saad S., Lloyd, Ricardo V., Szkudlinski, Mariusz W., Lapi, Suzanne E., Jaskula-Sztul, Renata
Format: Article
Language:English
Subjects:
Adenoma, Oxyphilic - diagnostic imaging
Adenoma, Oxyphilic - pathology
Animals
Cell Line, Tumor
Humans
Iodine
Iodine Radioisotopes
Male
Mice
Mice, Nude
Positron-Emission Tomography - methods
Receptors, Thyrotropin - metabolism
Thyroid Neoplasms - diagnostic imaging
Thyroid Neoplasms - pathology
Thyrotropin
Tissue Distribution
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Summary:Thyroid cancer is diagnosed in half a million people annually. Differentiated thyroid cancers (DTCs) make up 95% of these diagnoses. While clinical guidelines recommend surgical resection followed by radioactive iodine (RAI) ablation, loss of sodium-iodine symporter (NIS) expression causes up to 20% of DTCs to become RAI-refractory (RAI-R). For RAI-R patients, there is urgent need for new diagnostic and therapeutic approaches. This study evaluates the thyroid stimulating hormone receptor (TSHR) as a potential target for imaging DTC. Tissue microarrays (TMAs) containing 52 Hurthle cell carcinomas were immunostained to confirm TSHR expression. Recombinant human TSH (rhTSH) analogue superagonist TR1402 was radiolabeled with 89Zr (t1/2 = 78.4 h, β+ =22.7%) to produce [89Zr]Zr-TR1402. In vitro uptake assays were performed in high-TSHR expressing and low-TSHR expressing THJ529T and FTC133 thyroid cancer cell lines. In vivo PET/CT and biodistribution studies were performed in male athymic nude mice bearing TSHR-positive THJ529T tumors. Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were TSHR membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 found 38 ± 17% bound/mg in TSHR+ THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (p
ISSN:0039-6060
1532-7361
1532-7361
DOI:10.1016/j.surg.2023.05.045