Biparatopic anti-HER2 drug radioconjugates as breast cancer theranostics.

ABSTRACT:

Background

HER2 is overexpressed in 25-30% of breast cancer. Multiple domains targeting of a receptor can have synergistic/additive therapeutic effects.

Methods

Two domain-specific ADCs trastuzumab-PEG₆-DM1 (domain IV) and pertuzumab-PEG₆-DM1 (domain II) were developed, characterised and radiolabeled to obtain [⁸⁹Zr]Zr-trastuzumab-PEG₆-DM1 and [⁶⁷Cu]Cu-pertuzumab-PEG₆-DM1 to study their in vitro (binding assay, internalisation and cytotoxicity) and in vivo (pharmacokinetics, biodistribution and immunoPET/SPECT imaging) characteristics.

Results

The ADCs had an average drug-to-antibody ratio of 3. Trastuzumab did not compete with [⁶⁷Cu]Cu-pertuzumab-PEG₆-DM1 for binding to HER2. The

SUBMITTER: Ketchemen JP 

PROVIDER: S-EPMC10307858 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature