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In vitro evaluation of the monoclonal antibody 64Cu-IgG M75 against human carbonic anhydrase IX and its in vivo imaging
A. Čepa, J. Ráliš, V. Král, M. Paurová, J. Kučka, J. Humajová, M. Lázníček, O. Lebeda,
Language English Country England, Great Britain
Document type Evaluation Study, Journal Article
- MeSH
- Biological Transport, Active MeSH
- Antigens, Neoplasm immunology MeSH
- HT29 Cells MeSH
- NIH 3T3 Cells MeSH
- Immunoconjugates pharmacokinetics pharmacology MeSH
- Enzyme Inhibitors pharmacokinetics pharmacology MeSH
- Carbonic Anhydrase IX antagonists & inhibitors immunology MeSH
- Phosphinic Acids MeSH
- Humans MeSH
- Antibodies, Monoclonal pharmacokinetics pharmacology MeSH
- Mice, Nude MeSH
- Mice MeSH
- Neoplasms diagnostic imaging enzymology MeSH
- Positron Emission Tomography Computed Tomography MeSH
- Antineoplastic Agents, Immunological pharmacokinetics pharmacology MeSH
- Radiopharmaceuticals pharmacokinetics pharmacology MeSH
- Copper Radioisotopes pharmacokinetics pharmacology MeSH
- In Vitro Techniques MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
Specific oncology diagnostics requires new types of the selective radiopharmaceuticals, particularly those suitable for the molecular PET imaging. The aim of this work is to present a new, specific PET-immunodiagnostic radiopharmaceutical based on the monoclonal antibody IgG M75 targeting human carbonic anhydrase IX labelled with 64Cu (T½ = 12.70h) and its in vitro and in vivo evaluation. The antibody IgG M75 was conjugated with a non-commercial copper-specific chelator "phosphinate" and then labelled with the positron emitter 64Cu. Stability of the labelled conjugated was tested in human serum. The immunoreactivity of the labelled conjugate was evaluated in vitro on a suitable cell cultures of the colorectal carcinoma (HT-29) and its imaging properties were estimated in vivo on a mouse model with inoculated colorectal carcinoma HT-29 imaged on a µPET/CT. The tested radioimmunoconjugate was obtained in a specific activity of 0.25-0.5 MBq/µg. In vitro uptake experiments revealed specific binding to the HT-29 cells (45 ± 2.8% of the total added activity) and the measured KD value was found to be 9.2nM. Imaging clearly demonstrated significant uptake of the labelled monoclonal antibody in the tumour at 18h post administration. The radioimmunoconjugate 64Cu-PS-IgG M75 seems to be a suitable candidate for PET diagnostics of hypoxic tumours expressing human carbonic anhydrase IX.
Department of Inorganic Chemistry Faculty of Science Charles University Prague Czech Republic
Institute of Biophysics and Informatics 1st Medical Faculty Charles University Prague Czech Republic
Institute of Macromolecular Chemistry of the CAS Czech Republic
References provided by Crossref.org
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