Site-Specifically Labeled Antibody-Drug Conjugate for Simultaneous Therapy and ImmunoPET.

ABSTRACT: The conjugation of antibodies with cytotoxic drugs can alter their in vivo pharmacokinetics. As a result, the careful assessment of the in vivo behavior, and specifically the tumor-targeting properties, of antibody-drug conjugates represents a crucial step in their development. In order to facilitate this process, we have created a methodology that facilitates the dual labeling of an antibody with both a toxin and a radionuclide for positron emission tomography (PET). To minimize the impact of these modifications, this chemoenzymatic approach leverages strain-promoted azide-alkyne click chemistry to graft both cargoes to the heavy chain glycans of the immuoglobulin's F_c domain. As a proof-of-concept, a HER2-targeting trastuzumab immunoconjugate was created bearing both a monomet

SUBMITTER: Adumeau P 

PROVIDER: S-EPMC6466629 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature