| Autor: |
Magdalena Rodak, Yana Dekempeneer, Maria Wojewódzka, Vicky Caveliers, Peter Covens, Brian W. Miller, Matthijs B. Sevenois, Frank Bruchertseifer, Alfred Morgenstern, Tony Lahoutte, Matthias D'Huyvetter, Marek Pruszyński |
| Přispěvatelé: |
Supporting clinical sciences, Medical Imaging, Nuclear Medicine, UZB Other, Faculty of Medicine and Pharmacy |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Molecular cancer therapeutics. 21(12) |
| ISSN: |
1538-8514 |
| Popis: |
Human epidermal growth factor receptor type 2 (HER2) is overexpressed in various cancers; thus, HER2-targeting single-domain antibodies (sdAb) could offer a useful platform for radioimmunotherapy. In this study, we optimized the labeling of an anti-HER2-sdAb with the α-particle-emitter 225Ac through a DOTA-derivative. The formed radioconjugate was tested for binding affinity, specificity and internalization properties, whereas cytotoxicity was evaluated by clonogenic and DNA double-strand-breaks assays. Biodistribution studies were performed in mice bearing subcutaneous HER2pos tumors to estimate absorbed doses delivered to organs and tissues. Therapeutic efficacy and potential toxicity were assessed in HER2pos intraperitoneal ovarian cancer model and in healthy C57Bl/6 mice. [225Ac]Ac-DOTA-2Rs15d exhibited specific cell uptake and cell-killing capacity in HER2pos cells (EC50 = 3.9 ± 1.1 kBq/mL). Uptake in HER2pos lesions peaked at 3 hours (9.64 ± 1.69% IA/g), with very low accumulation in other organs ( |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
