title: Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics.
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 (18)F 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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA).
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rashidian
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA).
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA).
authors.forename: Jerre G
authors.initials: JG
authors.lastname: Edens
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA).
authors.forename: Johanne T
authors.initials: JT
authors.lastname: Jacobsen
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA).
authors.forename: Intekhab
authors.initials: I
authors.lastname: Hossain
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA).
authors.forename: Qifan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA).
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Victora
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA).
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142 (USA).
authors.forename: Hidde
authors.initials: H
authors.lastname: Ploegh
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, Boston, MA 02114 (USA).
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019281:Dimerization; D006207:Half-Life; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D057054:Molecular Imaging; D061905:Single-Domain Antibodies / Q000097:blood / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000949:Histocompatibility Antigens Class II; D061905:Single-Domain Antibodies
keywords: PEGylation; enzymes; isotopic labeling; positron emission tomography; single-domain antibodies