(99m)Tc-labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer

Thyroid. 2014 Aug;24(8):1297-308. doi: 10.1089/thy.2013.0429. Epub 2014 Jun 20.


Background: Differentiated thyroid carcinomas originating from thyroid follicular cells are frequent tumors of the thyroid with relatively good prognosis due to improved surgical techniques and follow-up procedures. Poorly differentiated thyroid cancers, which lose iodine uptake ability, in most cases still express thyrotropin (TSH) receptors (TSHR). Therefore, the aim of this study was to radiolabel a superagonist recombinant human TSH (rhTSH) analogue for imaging poorly differentiated thyroid cancer.

Methods: The TSHR superagonist, TR1401, was labeled with (99m)Tc using an indirect method via succinimidyl-6-hydrazinonicotinate hydrochloride conjugation. In vitro quality controls included SDS-PAGE, cysteine challenge, and cell-binding assay on TSHR positive cell lines (JP09 and ML-1). In vivo studies included tumor targeting experiments in athymic nude CD-1 mice xenografted with several different TSHR positive cells (JP09, K1, and ML-1) and TSHR negative cells (JP02) as control.

Results: The superagonist rhTSH analogue TR1401 was labeled with high labeling efficiency (>95%) and high specific activity (9250 MBq/mg). The labeled molecule retained its biologic activity and structural integrity. In tumor targeting experiments, a focal uptake of radiolabeled TR1401 was observed in TSHR positive cells but not in TSHR negative cells. The same observation was made in a dog with spontaneous intraglandular thyroid cancer.

Conclusions: We were able to radiolabel the rhTSH superagonist analogue TR1401 with (99m)Tc efficiently with retention of in vitro and in vivo binding capacity to TSHR. The relative role of such novel radiopharmaceutical versus (131)I scanning of thyroid cancer will require future histopathologic and clinical studies, but it may open new perspectives for presurgical staging of thyroid cancer, and diagnosis of radioiodine negative local relapses and/or distant metastases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cattle
  • Cell Differentiation
  • Cell Separation
  • Cricetinae
  • Cricetulus
  • Dogs
  • Flow Cytometry
  • Humans
  • Iodine / chemistry
  • Iodine Radioisotopes / therapeutic use
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Transplantation
  • Niacinamide / analogs & derivatives
  • Niacinamide / chemistry
  • Protein Binding
  • Radionuclide Imaging
  • Recombinant Proteins / chemistry
  • Succinimides / chemistry
  • Technetium / chemistry*
  • Thyroglobulin / metabolism
  • Thyroid Neoplasms / diagnostic imaging*
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology*
  • Thyroid Neoplasms / radiotherapy
  • Thyrotropin / analogs & derivatives
  • Thyrotropin / chemistry*


  • Iodine Radioisotopes
  • Recombinant Proteins
  • Succinimides
  • TR1401 peptide
  • succinimidyl 6-hydrazinonicotinate
  • Niacinamide
  • Technetium
  • Thyrotropin
  • Thyroglobulin
  • Iodine