Synthesis and preliminary in vitro evaluation of DOTA-Tenatumomab conjugates for theranostic applications in tenascin expressing tumors
| Autor: | Ferdinando Maria Milazzo, Fiorella Petronzelli, Antonio Rosi, Rita De Santis, Gianfranco Battistuzzi, Anna Maria Anastasi, Giuseppe Giannini, Loredana Leone, Claudio Albertoni, Laura Salvini, Lorenzo Tei |
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| Rok vydání: | 2019 |
| Předmět: |
Clinical Biochemistry
Pharmaceutical Science Tenascin 01 natural sciences Biochemistry Theranostic Nanomedicine chemistry.chemical_compound Heterocyclic Compounds 1-Ring Structure-Activity Relationship Antigen Neoplasms Drug Discovery DOTA Humans Molecular Biology Tenatumomab biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Biotinylation Radionuclide therapy biology.protein Molecular Medicine Conjugate |
| Zdroj: | Bioorganicmedicinal chemistry. 27(15) |
| ISSN: | 1464-3391 |
| Popis: | Tenatumomab is an anti-tenascin murine monoclonal antibody previously used in clinical trials for delivering radionuclides to tumors by both pre-targeting (biotinylated Tenatumomab within PAGRIT) and direct 131Iodine labeling approaches. Here we present the synthesis and in vitro characterization of three Tenatumomab conjugates to bifunctional chelating agents (NHS-DOTA, NCS-DOTA and NCS-DTPA). Results indicate ST8198AA1 (Tenatumomab-DOTAMA, derived by conjugation of NHS-DOTA), as the most promising candidate in terms of conjugation rate and yield, stability, antigen immunoreactivity and affinity. Labeling efficiency of the different chelators was investigated with a panel of cold metals indicating DOTAMA as the best chelator. Labeling of Tenatumomab-DOTAMA was then optimized with several metals and stability performed confirms suitability of this conjugate for further development. ST8198AA1 represents an improvement of the previous antibody forms because the labeling with radionuclides like 177Lu or 64Cu would allow theranostic applications in patients bearing tenascin expressing tumors. |
| Databáze: | OpenAIRE |
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