Development and characterization of an αvβ6-specific diabody and a disulfide-stabilized αvβ6-specific cys-diabody

Nuclear Medicine and Biology
Jason B WhiteJulie L Sutcliffe

Abstract

This work describes the development and characterization of two antibody fragments that specifically target the α(v)β(6) integrin, a non-covalent diabody and a disulfide-stabilized cys-diabody. The diabodies were analyzed for their ability to bind both immobilized and cell surface-bound α(v)β(6). Radiolabeling was done using non-site-specific and site-specific conjugation approaches with N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]-SFB) and the bifunctional chelator 1,4,7-triazacyclononane-triacetic acid maleimide (NOTA-maleimide) and copper-64 ([(64)Cu]), respectively. The affects of each radiolabeling method on RCY, RCP, and immunoreactivity were analyzed for the [(18)F]-FB-α(v)β(6) diabody, [(18)F]-FB-α(v)β(6) cys-diabody, and the [(64)Cu]-NOTA-α(v)β(6) cys-diabody. Diabodies were constructed from the variable domains of the humanized 6.3G9 anti-α(v)β(6) intact antibody. The anti-α(v(β(6) cys-diabody was engineered with C-terminal cysteines to enable covalent dimerization and site-specific modification. Biochemical characterization included SDS-PAGE, Western blot, and electrospray ionization to confirm MW, and flow cytometry and ELISA experiments were used to determine binding affinity and specificity to α(v)β(6). The dia...Continue Reading

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Citations

Apr 28, 2016·Expert Opinion on Drug Delivery·Sam MassaNick Devoogdt
Jan 24, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Paul FlechsigAnnette Altmann
Jun 28, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Jason B WhiteJulie L Sutcliffe
May 5, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Annette AltmannUwe Haberkorn

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