Noninvasive imaging of tumor progression, metastasis, and fibrosis using a nanobody targeting the extracellular matrix
Name
14181.full.pdf
Description
Published version
Size
2.6 MB
Format
Adobe PDF
Checksum (MD5)
8f1eae4570fa8020ffcd0857c1222660
Author(s)
Jailkhani, Noor
Ingram, Jessica R.
Rashidian, Mohammad
Rickelt, Steffen
Tian, Chenxi
Mak, Howard
Jiang, Zhigang
Ploegh, Hidde L.
Hynes, Richard O
Date Issued
May 2019
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Jailkhani, Noor et al. "Noninvasive imaging of tumor progression, metastasis, and fibrosis using a nanobody targeting the extracellular matrix." Proceedings of the National Academy of Sciences 116, 28 (July 2019): 14181-14190 © 2019 National Academy of Sciences
Version
Final published version
Abstract
Extracellular matrix (ECM) deposition is a hallmark of many diseases, including cancer and fibroses. To exploit the ECM as an imaging and therapeutic target, we developed alpaca-derived libraries of “nanobodies” against disease-associated ECM proteins. We describe here one such nanobody, NJB2, specific for an alternatively spliced domain of fibronectin expressed in disease ECM and neovasculature. We showed by noninvasive in vivo immuno-PET/CT imaging that NJB2 detects primary tumors and metastatic sites with excellent specificity in multiple models of breast cancer, including human and mouse triple-negative breast cancer, and in melanoma. We also imaged mice with pancreatic ductal adenocarcinoma (PDAC) in which NJB2 was able to detect not only PDAC tumors but also early pancreatic lesions called pancreatic intraepithelial neoplasias, which are challenging to detect by any current imaging modalities, with excellent clarity and signal-to-noise ratios that outperformed conventional 2-fluorodeoxyglucose PET/CT imaging. NJB2 also detected pulmonary fibrosis in a bleomycin-induced fibrosis model. We propose NJB2 and similar anti-ECM nanobodies as powerful tools for noninvasive detection of tumors, metastatic lesions, and fibroses. Furthermore, the selective recognition of disease tissues makes NJB2 a promising candidate for nanobody-based therapeutic applications.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.1817442116
