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Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer.
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.
Affiliation
  • Gimblet GR; Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL.
  • Whitt J; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.
  • Houson HA; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL.
  • Lin D; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
  • Guenter R; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL. Electronic address: https://twitter.com/rachaelguenter.
  • Rao TC; Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL.
  • Wang D; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
  • Ness J; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
  • Gonzalez ML; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
  • Murphy MS; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.
  • Gillis A; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.
  • Chen H; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL. Electronic address: https://twitter.com/herbchen.
  • Copland JA; Department of Cancer Biology, Mayo Clinic Jacksonville, Jacksonville, FL.
  • Kenderian SS; Division of Hematology, Mayo Clinic Rochester, Rochester, MN.
  • Lloyd RV; Department of Pathology, University of Wisconsin-Madison, Madison, WI.
  • Szkudlinski MW; Trophogen, Inc., Rockville, MD.
  • Lapi SE; Department of Radiology, University of Alabama at Birmingham, Birmingham, AL. Electronic address: https://twitter.com/lapisuzanne.
  • Jaskula-Sztul R; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL. Electronic address: rjsztul@uabmc.edu.
Surgery ; 175(1): 199-206, 2024 01.
Article in En | MEDLINE | ID: mdl-37919223
ABSTRACT

BACKGROUND:

Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer.

METHODS:

We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors.

RESULTS:

Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection.

CONCLUSION:

Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Thyrotropin / Thyroid Neoplasms / Adenoma, Oxyphilic / Iodine Limits: Animals / Humans / Male Language: En Journal: Surgery Year: 2024 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Thyrotropin / Thyroid Neoplasms / Adenoma, Oxyphilic / Iodine Limits: Animals / Humans / Male Language: En Journal: Surgery Year: 2024 Document type: Article Country of publication: United States