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Published on: January 29, 2019
Tissue Factor-Targeted ImmunoPET Imaging and Radioimmunotherapy of Anaplastic Thyroid Cancer
Weijun Wei1,2, Qiufang Liu3, Dawei Jiang2
1Department of Nuclear Medicine Institute of Clinical Nuclear Medicine Renji Hospital, School of Medicine Shanghai Jiao Tong University State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute 1630 Dongfang Rd Shanghai 200127 China.
Abstract:
Anaplastic thyroid cancer (ATC) is the most aggressive subtype of thyroid cancers with a dismal prognosis. It is aimed to explore a new biomarker and devise a marker-dependent theranostic pair for ATC. Flow cytometry is used to determine tissue factor (TF) expression in thyroid cancer cell lines. ALT-836, a TF-specific monoclonal antibody, is radiolabeled with 64Cu to develop 64Cu-NOTA-ALT-836. The diagnostic utility is assessed by immuno-positron emission tomography (immunoPET) imaging in ATC models. To facilitate total surgical removal of orthotopic ATCs, a near-infrared fluorescent imaging probe IRDye 800CW-ALT-836 is designed. As the therapeutic component, 131I-ALT-836 is further developed and the radioimmunotherapy (RIT) efficacy of this agent is interrogated in orthotopic ATC models. The results demonstrate that TF is highly expressed on the ATC cell line THJ-16T. 64Cu-NOTA-ALT-836 immunoPET imaging clearly delineates both subcutaneous and orthotopic ATCs, with a peak tumor uptake of 19.93 ± 2.17% ID per g (n = 3) and 37.20 ± 1.71% ID per g (n = 3), respectively. Fluorescent imaging with IRDye 800CW-ALT-836 facilitates the total resection of orthotopic ATCs. Moreover, 131I-ALT-836 RIT prolongs the survival of ATC-bearing mice. Taken together, TF is a promising marker for ATC and successive use of 64Cu-NOTA-ALT-836 and 131I-ALT-836 can realize precise management of ATC.
Insights
Tissue factor (TF) is a promising biomarker for aggressive anaplastic thyroid cancer (ATC). Researchers developed a TF-targeted theranostic pair, enabling precise diagnosis and treatment of ATC models, improving survival.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Anaplastic thyroid cancer (ATC) is highly aggressive with poor outcomes.
- Identifying effective biomarkers and targeted therapies for ATC is critical.
Purpose of the Study:
- To explore tissue factor (TF) as a biomarker for ATC.
- To develop a theranostic pair for ATC management based on TF.
Main Methods:
- Flow cytometry to assess TF expression in ATC cell lines.
- Development of 64Cu-NOTA-ALT-836 for diagnostic immunoPET imaging.
- Design of IRDye 800CW-ALT-836 for fluorescent imaging-guided surgery.
- Development of 131I-ALT-836 for radioimmunotherapy (RIT).
Main Results:
- TF is highly expressed on the ATC cell line THJ-16T.
- 64Cu-NOTA-ALT-836 effectively visualized both subcutaneous and orthotopic ATCs via immunoPET.
- IRDye 800CW-ALT-836 facilitated complete surgical resection of orthotopic ATCs.
- 131I-ALT-836 RIT significantly prolonged survival in ATC-bearing mice.
Conclusions:
- TF is a viable biomarker for anaplastic thyroid cancer.
- The developed theranostic pair (64Cu-NOTA-ALT-836, IRDye 800CW-ALT-836, 131I-ALT-836) offers precise diagnosis, surgical guidance, and therapeutic intervention for ATC.
