DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, So-Young | ko |
dc.contributor.author | Hong, Young-Don | ko |
dc.contributor.author | Kim, Hak-Sung | ko |
dc.contributor.author | Choi, Sun-Ju | ko |
dc.date.accessioned | 2013-08-08T01:52:27Z | - |
dc.date.available | 2013-08-08T01:52:27Z | - |
dc.date.created | 2013-04-26 | - |
dc.date.created | 2013-04-26 | - |
dc.date.issued | 2013-04 | - |
dc.identifier.citation | NUCLEAR MEDICINE AND BIOLOGY, v.40, no.3, pp.424 - 429 | - |
dc.identifier.issn | 0969-8051 | - |
dc.identifier.uri | http://hdl.handle.net/10203/174148 | - |
dc.description.abstract | Introduction: For the development of safe and effective protein-based radiolabeled complexes such as radioimmunotherapy (RIT), the selection of the radionuclides and the chelating agents used for the radiolabeling of tumor-targeting molecules is a critical factor. We aim to synthesize a novel bifunctional chelating agent containing the isothiocyanate group for easy conjugation with antibodies having the characteristics of high stable chelation with therapeutic radionuclides, Methods: We have synthesized the DTPA analogue retaining L-cysteine as a core ligand of the thiol group. The chelating power of cysteine-based DTPA-NCS (cys-DTPA-NCS) was compared with that of commercial rho-SCN-Bn-DTPA. In an application, the cetuximab was radioimmunoconjugated with Lu-177 using cys-DTPA-NCS. The affinity was tested in a cell line overexpressing EGFR. A therapy study was conducted in nude mice with subcutaneous HT-29 xenografts. Results: The cys-DTPA-NCS presents an excellent ability to chelate as compared to the rho-SCN-Bn-DTPA. For mean ratio chemical labeling yields of 95%, the result was 0.97. Lu-177-cys-DTPA-NCS-cetuximab was prepared under ambient condition with a high radiolabeling yield and the radiochemical purity was sustained for at least 6 days. The IC50 value of the Lu-177-labeled cetuximab was 10 nM (95% confidence). The stability and therapeutic efficacy of the candidate radiopharmaceutical were verified. Conclusion: The new DTPA derivative, cys-DTPA-NCS, is a good bifunctional chelating agent that can be used for protein-based radiopharmaceutical using lanthanides such as Lu-177 and Y-90. The prepared Lu-177-cys-DTPA-NCS-cetuximab can be used for the diagnosis and treatment of human colorectal tumor. (C) 2013 Elsevier Inc. All rights reserved. | - |
dc.language | English | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.subject | MONOCLONAL-ANTIBODY | - |
dc.subject | RADIONUCLIDE THERAPY | - |
dc.subject | XENOGRAFT | - |
dc.subject | CETUXIMAB | - |
dc.subject | CANCER | - |
dc.subject | EGFR | - |
dc.subject | PET | - |
dc.title | Synthesis and application of a novel cysteine-based DTPA-NCS for targeted radioimmunotherapy | - |
dc.type | Article | - |
dc.identifier.wosid | 000316507400017 | - |
dc.identifier.scopusid | 2-s2.0-84875264089 | - |
dc.type.rims | ART | - |
dc.citation.volume | 40 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 424 | - |
dc.citation.endingpage | 429 | - |
dc.citation.publicationname | NUCLEAR MEDICINE AND BIOLOGY | - |
dc.identifier.doi | 10.1016/j.nucmedbio.2012.12.007 | - |
dc.contributor.localauthor | Kim, Hak-Sung | - |
dc.contributor.nonIdAuthor | Hong, Young-Don | - |
dc.contributor.nonIdAuthor | Choi, Sun-Ju | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Radioimmunotherapy | - |
dc.subject.keywordAuthor | Bifunctional Chelating agent | - |
dc.subject.keywordAuthor | DTPA derivative | - |
dc.subject.keywordAuthor | Radionuclide | - |
dc.subject.keywordAuthor | Lutetium-177 (Lu-177) | - |
dc.subject.keywordAuthor | Cetuximab | - |
dc.subject.keywordPlus | MONOCLONAL-ANTIBODY | - |
dc.subject.keywordPlus | RADIONUCLIDE THERAPY | - |
dc.subject.keywordPlus | XENOGRAFT | - |
dc.subject.keywordPlus | CETUXIMAB | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | EGFR | - |
dc.subject.keywordPlus | PET | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.