Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics
Dr. Mohammad Rashidian
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
These authors contributed equally.
Search for more papers by this authorLu Wang
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
These authors contributed equally.
Search for more papers by this authorJerre G. Edens
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorDr. Johanne T. Jacobsen
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorIntekhab Hossain
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorQifan Wang
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorDr. Gabriel D. Victora
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Neil Vasdev
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Hidde Ploegh, Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Steven H. Liang, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Hidde Ploegh
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142 (USA)
Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Hidde Ploegh, Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Steven H. Liang, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Steven H. Liang
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Hidde Ploegh, Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Steven H. Liang, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorDr. Mohammad Rashidian
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
These authors contributed equally.
Search for more papers by this authorLu Wang
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
These authors contributed equally.
Search for more papers by this authorJerre G. Edens
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorDr. Johanne T. Jacobsen
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorIntekhab Hossain
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorQifan Wang
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorDr. Gabriel D. Victora
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Neil Vasdev
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Hidde Ploegh, Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Steven H. Liang, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Hidde Ploegh
Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142 (USA)
Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Hidde Ploegh, Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Steven H. Liang, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorCorresponding Author
Prof. Dr. Steven H. Liang
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Neil Vasdev, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Hidde Ploegh, Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA)
Steven H. Liang, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA)
Search for more papers by this authorGraphical Abstract
Improve your image! Dual labeling of antibody fragments with a fluorophore or 18F isotope for multimodal imaging and with a PEG moiety or a second antibody fragment to improve circulatory half-life or avidity led to constructs that recognized Class II MHC products (see picture) and CD11b with high specificity. PET imaging with the constructs enabled the detection of tumors as small as a few millimeters in size.
Abstract
Antibodies are currently the fastest-growing class of therapeutics. Although naked antibodies have proven valuable as pharmaceutical agents, they have some limitations, such as low tissue penetration and a long circulatory half-life. They have been conjugated to toxic payloads, PEGs, or radioisotopes to increase and optimize their therapeutic efficacy. Although nonspecific conjugation is suitable for most in vitro applications, it has become evident that site specifically modified antibodies may have advantages for in vivo applications. Herein we describe a novel approach in which the antibody fragment is tagged with two handles: one for the introduction of a fluorophore or 18F isotope, and the second for further modification of the fragment with a PEG moiety or a second antibody fragment to tune its circulatory half-life or its avidity. Such constructs, which recognize Class II MHC products and CD11b, showed high avidity and specificity. They were used to image cancers and could detect small tumors.
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