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Development and characterization of CD54-targeted immunoPET imaging in solid tumors

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Abstract

Purpose

Intercellular adhesion molecule-1 (ICAM-1, CD54) is an emerging therapeutic target for a variety of solid tumors including melanoma and anaplastic thyroid cancer (ATC). This study aims to develop an ICAM-1-targeted immuno-positron emission tomography (immunoPET) imaging strategy and assess its diagnostic value in melanoma and ATC models.

Methods

Flow cytometry was used to screen ICAM-1-positive melanoma and ATC cell lines. Melanoma and ATC models were established using A375 cell line and THJ-16T cell line, respectively. An ICAM-1-specific monoclonal antibody (R6-5-D6) and a nonspecific human IgG were radiolabeled with 64Cu and the diagnostic efficacies were interrogated in tumor-bearing mouse models. Biodistribution and fluorescent imaging studies were performed to confirm the specificity of the ICAM-1-targeted imaging probes.

Results

ICAM-1 was strongly expressed on melanoma and advanced thyroid cancer cell lines. 64Cu-NOTA-ICAM-1 immunoPET imaging efficiently delineated A375 melanomas with a peak tumor uptake of 21.28 ± 6.56 %ID/g (n = 5), significantly higher than that of 64Cu-NOTA-IgG (10.63 ± 2.58 %ID/g, n = 3). Moreover, immunoPET imaging with 64Cu-NOTA-ICAM-1 efficiently visualized subcutaneous and orthotopic ATCs with high clarity and contrast. Fluorescent imaging with IRDye 800CW-ICAM-1 also visualized orthotopic ATCs and the tumor uptake could be blocked by the ICAM-1 parental antibody R6-5-D6, indicating the high specificity of the developed probe. Finally, blocking with the human IgG prolonged the circulation of the 64Cu-NOTA-ICAM-1 in R2G2 mice without compromising the tumor uptake.

Conclusion

ICAM-1-targeted immunoPET imaging could characterize ICAM-1 expression in melanoma and ATC, which holds promise for optimizing ICAM-1-targeted therapies in the future.

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Acknowledgments

We appreciate Dr. Hao Yang and Prof. Gang Huang (Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences) for their help in acquiring fluorescent imaging data.

Funding

This work was supported, in part, by the University of Wisconsin – Madison, the National Institutes of Health (P30CA014520), and the Natural Science Foundation of China (81771858).

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Author notes

  1. Weijun Wei and Dawei Jiang contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China

    Weijun Wei & Jianjun Liu

  2. Departments of Radiology and Medical Physics, University of Wisconsin – Madison, Room 7137, 1111 Highland Avenue, Madison, WI, 53705-2275, USA

    Weijun Wei, Dawei Jiang, Miao Li, Christopher J. Kutyreff, Jonathan W. Engle & Weibo Cai

  3. School of Pharmacy, University of Wisconsin – Madison, Room 7137, 1111 Highland Avenue, Madison, WI, 53705-2275, USA

    Hye Jin Lee & Weibo Cai

  4. Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an, 710061, Shanxi, China

    Miao Li

  5. University of Wisconsin Carbone Cancer Center, Madison, WI, 53705, USA

    Weibo Cai

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  1. Weijun Wei
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Wei, W., Jiang, D., Lee, H.J. et al. Development and characterization of CD54-targeted immunoPET imaging in solid tumors. Eur J Nucl Med Mol Imaging 47, 2765–2775 (2020). https://doi.org/10.1007/s00259-020-04784-0

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