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

Weijun Wei,Weibo Cai,Jonathan W Engle,Qiufang Liu,Jianjun Liu,Christopher J Kutyreff,Haitao Zhao,Dawei Jiang

doi:10.1002/advs.201903595

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.

Highlights

IntroductionFlow cytometry is used to determine tissue factor (TF) expression in thyroid cancer cell lines
The results showed five of the six included cell lines were tissue factor (TF)-positive, including two Anaplastic thyroid cancer (ATC) cell lines (THJ-16T and 8505C) and three follicular thyroid cancer cell lines (FTC-133, FTC-236, and FTC-238)
Motivated by the prominent tumor uptake of 64Cu-NOTAALT-836 and IRDye 800 CW-ALT-836, we further developed 131I-ALT-836 and explored the effect of 131I-ALT-836 RIT in orthotopic ATC models. 131I-labeling of ALT-836 resulted in an overall labeling yield of 64.44 ± 0.08% (n = 3)

Summary

Introduction

Flow cytometry is used to determine tissue factor (TF) expression in thyroid cancer cell lines. Recent progress in understanding the molecular pathogenesis of thyroid cancers has led to the clinical translation of molecularly targeted therapies.[2–4]. To facilitate total fects and drug resistance associated with surgical removal of orthotopic ATCs, a near-infrared fluorescent imaging these regimens limit their broad clinical approbe IRDye 800CW-ALT-836 is designed. 131I-ALT-836 is further developed and the radioimmunotherapy (RIT) efficacy of this agent is interrogated in orthotopic ATC models. Fluorescent imaging with IRDye 800CW-ALT-836 facilitates the total resection of orthotopic ATCs. 131I-ALT-836 RIT prolongs the dine therapy due to loss of sodium iodide symporter (NIS). Along with the above progress, continuous attempts have been made to re-differentiate ATC to enhance NIS uptake,[10] but the clinical effect of survival of ATC-bearing mice. Introduction therapy, practical challenges lie in how to efficiently stratify patients before drug administration and how to precisely monitor

Results

Discussion

Conclusion