We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Preclinical screening of anti-HER2 nanobodies for molecular imaging of breast cancer.
- Authors
Vaneycken, Ilse; Devoogdt, Nick; Van Gassen, Naomi; Vincke, Cécile; Xavier, Catarina; Wernery, Ulrich; Muyldermans, Serge; Lahoutte, Tony; Caveliers, Vicky
- Abstract
Accurate determination of tumor human epidermal growth factor receptor 2 (HER2)-status in breast cancer patients is possible via noninvasive imaging, provided adequate tracers are used. In this study, we describe the generation of a panel of 38 nanobodies, small HER2-binding fragments that are derived from heavy-chain-only antibodies raised in an immunized dromedary. In search of a lead compound, a subset of nanobodies was biochemically characterized in depth and preclinically tested for use as tracers for imaging of xenografted tumors. The selected compound, 2Rs15d, was found to be stable and to interact specifically with HER2 recombinant protein and HER2-expressing cells in ELISA, surface plasmon resonance, flow cytometry, and radioligand binding studies with low nanomolar affinities, and did not compete with anti-HER2 therapeutic antibodies trastuzumab and pertuzumab. Single-photon-emission computed tomography (SPECT) imaging quantification and biodistribution analyses showed that 99mTc-labeled 2Rs15d has a high tumor uptake in 2 HER2+ tumor models, fast blood clearance, low accumulation in nontarget organs except kidneys, and high concomitant tumor-to-blood and tumor-to-muscle ratios at 1 h after intravenous injection. These values were dramatically lower for an irrelevant control 99mTc-nanobody and for 99mTc-2Rs15d targeting a HER2- tumor.
- Subjects
HER2 protein; BREAST cancer; TRACERS (Biology); IMMUNOGLOBULINS; TUMORS
- Publication
FASEB Journal, 2011, Vol 25, Issue 7, p2433
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.10-180331