Radiolabeling of antibody for epitope of human carbonic anhydrase IX (IgG M75) by 61Cu and 64Cu and its biological testing

0450524 - ÚJF 2016 RIV US eng A - Abstrakt
Čepa, Adam - Ráliš, Jan - Pavelka, A. - Marešová, L. - Kleinová, M. - Seifert, Daniel - Sieglová, Irena - Král, Vlastimil - Polášek, Miloslav - Lebeda, Ondřej - Paúrová, M. - Lázníček, M.
Radiolabeling of antibody for epitope of human carbonic anhydrase IX (IgG M75) by 61Cu and 64Cu and its biological testing.
European Journal of Nuclear Medicine and Molecular Imaging. Springer. Roč. 42, S (2015), s. 465-466. ISSN 1619-7070. E-ISSN 1619-7089.
[28th Annual congress of the European-Association-of-Nuclear-Medicine (EANM). 10.10.2015-14.10.2015, Hamburg]
Grant CEP: GA TA ČR TA02010797; GA MŠMT(CZ) LM2011019
Institucionální podpora: RVO:61389005 ; RVO:68378050
Klíčová slova: antibodies * Cu-61 * Cu-64
Kód oboru RIV: BG - Jaderná, atomová a mol. fyzika, urychlovače; EB - Genetika a molekulární biologie (UMG-J)

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.
Trvalý link: http://hdl.handle.net/11104/0251815