Noninvasive imaging of immune responses
Name
Rashidian-2015-Noninvasive imaging.pdf
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Author(s)
Rashidian, Mohammad
Keliher, Edmund J.
Bilate, Angelina M.
Duarte, Joao N.
Wojtkiewicz, Gregory R.
Jacobsen, Johanne Tracey
Cragnolini, Juanjo
Swee, Lee Kim
Victora, Gabriel D.
Weissleder, Ralph
Date Issued
May 2015
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Rashidian, Mohammad, Edmund J. Keliher, Angelina M. Bilate, Joao N. Duarte, Gregory R. Wojtkiewicz, Johanne Tracey Jacobsen, Juanjo Cragnolini, et al. “Noninvasive Imaging of Immune Responses.” Proc Natl Acad Sci USA 112, no. 19 (April 20, 2015): 6146–6151.
Version
Final published version
Abstract
At their margins, tumors often contain neutrophils, dendritic cells, and activated macrophages, which express class II MHC and CD11b products. The interplay between stromal cells, tumor cells, and migratory cells such as lymphocytes creates opportunities for noninvasive imaging of immune responses. We developed alpaca-derived antibody fragments specific for mouse class II MHC and CD11b products, expressed on the surface of a variety of myeloid cells. We validated these reagents by flow cytometry and two-photon microscopy to obtain images at cellular resolution. To enable noninvasive imaging of the targeted cell populations, we developed a method to site-specifically label VHHs [the variable domain (V[subscript H]) of a camelid heavy-chain only antibody] with [superscript 18]F or [superscript 64]Cu. Radiolabeled VHHs rapidly cleared the circulation (t[subscript 1/2] ≈ 20 min) and clearly visualized lymphoid organs. We used VHHs to explore the possibility of imaging inflammation in both xenogeneic and syngeneic tumor models, which resulted in detection of tumors with remarkable specificity. We also imaged the infiltration of myeloid cells upon injection of complete Freund’s adjuvant. Both anti-class II MHC and anti-CD11b VHHs detected inflammation with excellent specificity. Given the ease of manufacture and labeling of VHHs, we believe that this method could transform the manner in which antitumor responses and/or infectious events may be tracked.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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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.
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DOI of Published Version
https://doi.org/10.1073/pnas.1502609112
