Tissue Factor-Targeted ImmunoPET Imaging and Radioimmunotherapy of Anaplastic Thyroid Cancer

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.