| Autor: |
Vorobyeva, Sergey M. Deyev, Tianqi Xu, Yongsheng Liu, Alexey Schulga, Elena Konovalova, Javad Garousi, Sara S. Rinne, Maria Larkina, Haozhong Ding, Torbjörn Gräslund, Anna Orlova, Vladimir Tolmachev, Anzhelika |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cancers; Volume 13; Issue 14; Pages: 3589 |
| ISSN: |
2072-6694 |
| DOI: |
10.3390/cancers13143589 |
| Popis: |
The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40–60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an N- or C-terminal cysteine, were produced, site-specifically conjugated to a DOTA chelator and labeled with cobalt-57, gallium-68 or indium-111. Site-specific radioiodination was performed using ((4-hydroxyphenyl)-ethyl)maleimide (HPEM). Biodistribution of eight radiolabeled Ec1-probes was measured in nude mice bearing PCa DU145 xenografts. In all cases, positioning of a label at the C-terminus provided the best tumor-to-organ ratios. The non-residualizing [125I]I-HPEM label provided the highest tumor-to-muscle and tumor-to-bone ratios and is more suitable for EpCAM imaging in early-stage PCa. Among the radiometals, indium-111 provided the highest tumor-to-blood, tumor-to-lung and tumor-to-liver ratios and could be used at late-stage PCa. In conclusion, label position and composition are important for the DARPin Ec1. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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