Development and characterization of CD54-targeted immunoPET imaging in solid tumors
- PDF / 957,606 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 41 Downloads / 175 Views
ORIGINAL ARTICLE
Development and characterization of CD54-targeted immunoPET imaging in solid tumors Weijun Wei 1,2 & Dawei Jiang 2 & Hye Jin Lee 3 & Miao Li 2,4 & Christopher J. Kutyreff 2 & Jonathan W. Engle 2 & Jianjun Liu 1 & Weibo Cai 2,3,5 Received: 11 November 2019 / Accepted: 20 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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-NOTAICAM-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. Keywords ICAM-1 . ImmunoPET . Companion diagnostics . Thyroid cancer . Melanoma
Weijun Wei and Dawei Jiang contributed equally to this work. This article is part of the Topical Collection on Preclinical Imaging Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00259-020-04784-0) contains supplementary material, which is available to authorized users. * Jianjun Liu [email protected]
3
School of Pharmacy, University of Wisconsin – Madison, Room 7137, 1111 Highland Avenue, Madison, WI 53705-2275, USA
4
Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an 710061, Shanxi, China
5
University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA
* Weibo Cai [email protected] 1
Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong Universit
Data Loading...
