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Radiolabeling of antibody for epitope of human carbonic anhydrase IX (IgG M75) by 61Cu and 64Cu and its biological testing
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SYSNO ASEP 0450524 Document Type A - Abstract R&D Document Type O - Ostatní Title Radiolabeling of antibody for epitope of human carbonic anhydrase IX (IgG M75) by 61Cu and 64Cu and its biological testing Author(s) Čepa, Adam (UJF-V)
Ráliš, Jan (UJF-V) SAI
Pavelka, A. (CZ)
Marešová, L. (CZ)
Kleinová, M. (CZ)
Seifert, Daniel (UJF-V) ORCID
Sieglová, Irena (UMG-J)
Král, Vlastimil (UMG-J) RID
Polášek, Miloslav (UJF-V)
Lebeda, Ondřej (UJF-V) RID, ORCID, SAI
Paúrová, M. (CZ)
Lázníček, M. (CZ)Number of authors 12 Source Title European Journal of Nuclear Medicine and Molecular Imaging. - : Springer - ISSN 1619-7070
Roč. 42, S (2015), s. 465-466Number of pages 2 s. Publication form Print - P Action 28th Annual congress of the European-Association-of-Nuclear-Medicine (EANM) Event date 10.10.2015-14.10.2015 VEvent location Hamburg Country DE - Germany Event type EUR Language eng - English Country US - United States Keywords antibodies ; Cu-61 ; Cu-64 Subject RIV BG - Nuclear, Atomic and Molecular Physics, Colliders Subject RIV - cooperation Institute of Molecular Genetics - Genetics ; Molecular Biology R&D Projects TA02010797 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) LM2011019 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UJF-V - RVO:61389005 ; UMG-J - RVO:68378050 UT WOS 000363013202432 Annotation Human carbonic anhydrase IX is a membrane enzyme that is significantly expressed in some types of cancer cells. The antibody IgG M75 was successfully conjugated with a new, copper-specific chelator “phosphinate”, the conjugation method was optimized and is well-reproducible. The conjugate was then labelled with two positron emitting copper radioisotopes, Cu-61 (3.333 h) and Cu-64 (12.701 h). Labelled conjugates were tested in vivo in mice with colorectal cancer xenografts. Copper radioisotopes were produced via Ni-nat(d,x) and Ni-64(p,n) reactions (Ni, 99.999 %, Goodfellow; Ni-64, 99.09 %, Isoflex). Specific activity of Cu-61 was 1 GBq/mg Cu and more, which was satisfactory for the labelling purposes. All reagents were analytical grade and were purified prior labelling with chelex-100 in sodium form, 100-200 mesh from metals surplus. Chelator “phospinate” was synthesized and characterized in our laboratories. Antibody IgG M75 was prepared by genetic engineering methods. Immunoconjugates (IgG M75-SCN-phospinate) were separated with use of PD 10 Desalting Columns and analyzed using size exclusion chromatography column BioSep SEC-S-3000. The conjugate M75-SCN-phosphinate was labelled successfully with both Cu-61 (96% yield) and Cu-64 (97% yield). Biodistribution experiments revealed high uptake of both labelled compounds in tumour tissue: Cu-61-labelled conjugate showed uptake of about 10 % ID/g after 6 hours, while Cu-64-labeled about 24 % ID/g even after 48 hours. The labelling resulted in the product of high specific activity (1.0 and 7.4 MBq/microgram, respectively) and of high radiochemical purity (> 95 %). The labelled molecule has considerable potential as a radioimmunopharmaceutical suitable for imaging of tumors expressing carbonic anhydrase IX by positron emission tomography. Workplace Nuclear Physics Institute Contact Markéta Sommerová, sommerova@ujf.cas.cz, Tel.: 266 173 228 Year of Publishing 2016
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