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Noninvasive imaging of immune responses.

Authors
  • Rashidian, Mohammad1
  • Keliher, Edmund J2
  • Bilate, Angelina M3
  • Duarte, Joao N3
  • Wojtkiewicz, Gregory R4
  • Jacobsen, Johanne Tracey5
  • Cragnolini, Juanjo3
  • Swee, Lee Kim3
  • Victora, Gabriel D3
  • Weissleder, Ralph6
  • Ploegh, Hidde L7
  • 1 Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;
  • 2 Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Radiology, Massachusetts General Hospital, Boston, MA 02114;
  • 3 Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
  • 4 Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114;
  • 5 Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Center for Immune Regulation, Oslo University Hospital, University of Oslo, N-0372 Oslo, Norway; , (Norway)
  • 6 Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Radiology, Massachusetts General Hospital, Boston, MA 02114; and Department of Systems Biology, Harvard Medical School, Boston, MA 02115.
  • 7 Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142; [email protected]
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
May 12, 2015
Volume
112
Issue
19
Pages
6146–6151
Identifiers
DOI: 10.1073/pnas.1502609112
PMID: 25902531
Source
Medline
Keywords
License
Unknown

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 (VH) of a camelid heavy-chain only antibody] with (18)F or (64)Cu. Radiolabeled VHHs rapidly cleared the circulation (t1/2 ≈ 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.

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