Dataset Information

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.

SUBMITTER: Wei W

PROVIDER: S-EPMC7341097 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Wei Weijun W Liu Qiufang Q Jiang Dawei D Zhao Haitao H Kutyreff Christopher J CJ Engle Jonathan W JW Liu Jianjun J Cai Weibo W

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200517 13

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 <sup>64</sup>Cu to develop <sup>64</sup>Cu-NOTA-ALT-836. The diagnostic utility is assessed by immuno-positron emission tomography (immun ...[more]

PMID: 32670751

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Project description:Overexpression of tissue factor (TF) has been associated with increased tumor growth, tumor angiogenesis, and metastatic potential in many malignancies, including pancreatic cancer. Additionally, high TF expression was shown to strongly correlate with poor prognoses and decreased survival in pancreatic cancer patients. Herein, we exploited the potential targeting of TF for positron emission tomography (PET) imaging of pancreatic cancer. The TF-targeted tracer was developed through radiolabeling of the anti-human TF monoclonal antibody (ALT-836) with 89Zr. The tracer was characterized by fluorescence microscopy and flow cytometry assays in BXPC-3 and PANC-1 cells, two pancreatic cancer cell lines with high and low TF expression levels, respectively. Non-invasive PET scans were acquired in tumor-bearing mice injected with 89Zr-Df-ALT-836. Additionally, ex vivo biodistribution, blocking, and histological studies were performed to establish the affinity and specificity of 89Zr-Df-ALT-836 for TF in vivo. 89Zr-labeling of Df-ALT-836 was achieved in high yield and good specific activity. Flow cytometry and microscopy studies revealed no detectable difference in TF-binding affinity between ALT-836 and Df-ALT-836 in vitro. Longitudinal PET scans unveiled a lasting and prominent 89Zr-Df-ALT-836 uptake in BXPC-3 tumors (peak at 31.5±6.0%ID/g at 48h post-injection; n=3), which was significantly abrogated (2.3±0.5%ID/g at 48h post-injection; n=3) when mice were pre-injected with a blocking dose (50mg/kg) of unlabeled ALT-836. Ex vivo biodistribution data confirmed the accuracy of the PET results, and histological analysis correlated high tumor uptake with in situ TF expression. Taken together, these results attest to the excellent affinity and TF-specificity of 89Zr-Df-ALT-836. With elevated, persistent, and specific accumulation in TF-positive BXPC-3 tumors, PET imaging using 89Zr-Df-ALT-836 promises to open new avenues for improving future diagnosis, stratification, and treatment response assessment in pancreatic cancer patients.

Dataset Information

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

Publications

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

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