99mTc-Labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer

Filippo Galli, Isabella Manni, Giulia Piaggio, Lajos Balogh, Bruce D. Weintraub, Mariusz W. Szkudlinski, Valerie Fremont, Rudi A J O Dierckx, Alberto Signore

Research output: Contribution to journalArticle

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Abstract

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 99mTc 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 (9250MBq/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 99mTc efficiently with retention of in vitro and in vivo binding capacity to TSHR. The relative role of such novel radiopharmaceutical versus 131I 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.

Original languageEnglish
Pages (from-to)1297-1308
Number of pages12
JournalThyroid
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 1 2014

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Thyrotropin Alfa
Thyrotropin Receptors
Thyroid Neoplasms
Neoplasms
Radiopharmaceuticals
Iodine
Quality Control
Cysteine
Polyacrylamide Gel Electrophoresis
Thyroid Gland
Observation
Dogs

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Galli, F., Manni, I., Piaggio, G., Balogh, L., Weintraub, B. D., Szkudlinski, M. W., ... Signore, A. (2014). 99mTc-Labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer. Thyroid, 24(8), 1297-1308. https://doi.org/10.1089/thy.2013.0429

99mTc-Labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer. / Galli, Filippo; Manni, Isabella; Piaggio, Giulia; Balogh, Lajos; Weintraub, Bruce D.; Szkudlinski, Mariusz W.; Fremont, Valerie; Dierckx, Rudi A J O; Signore, Alberto.

In: Thyroid, Vol. 24, No. 8, 01.08.2014, p. 1297-1308.

Research output: Contribution to journalArticle

Galli, F, Manni, I, Piaggio, G, Balogh, L, Weintraub, BD, Szkudlinski, MW, Fremont, V, Dierckx, RAJO & Signore, A 2014, '99mTc-Labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer', Thyroid, vol. 24, no. 8, pp. 1297-1308. https://doi.org/10.1089/thy.2013.0429
Galli, Filippo ; Manni, Isabella ; Piaggio, Giulia ; Balogh, Lajos ; Weintraub, Bruce D. ; Szkudlinski, Mariusz W. ; Fremont, Valerie ; Dierckx, Rudi A J O ; Signore, Alberto. / 99mTc-Labeled-rhTSH analogue (TR1401) for imaging poorly differentiated metastatic thyroid cancer. In: Thyroid. 2014 ; Vol. 24, No. 8. pp. 1297-1308.
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AU - Piaggio, Giulia

AU - Balogh, Lajos

AU - Weintraub, Bruce D.

AU - Szkudlinski, Mariusz W.

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AU - Dierckx, Rudi A J O

AU - Signore, Alberto

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AB - 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 99mTc 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 (9250MBq/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 99mTc efficiently with retention of in vitro and in vivo binding capacity to TSHR. The relative role of such novel radiopharmaceutical versus 131I 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.

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