Human carbonic anhydrase IX is a membrane enzyme that is significantly expressed in some types of cancer cells, while copper radioisotopes offer wide range of diagnostic, therapeutic and theranostic properties. The work was focused on a new approach to the labelling of antibody IgG M75 for epitope human carbonic anhydrase IX with copper radioisotopes 61Cu and 64Cu and its in vivo testing in mice with inoculated colorectal cancer. Monoclonal antibody IgG M75 for epitope human carbonic anhydrase IX was successfully conjugated with copper-specific chelator "phosphinate" and labelled with 61Cu and 64Cu The obtained molecule has considerable potential as a radioimmuno pharmaceutical suitable for imaging of tumours expressing carbonic anhydrase IX by positron emission tomography (PET).
- MeSH
- antigeny nádorové imunologie MeSH
- buňky HT-29 MeSH
- imunoglobulin G chemie MeSH
- imunokonjugáty chemie farmakokinetika MeSH
- karboanhydrasa IX imunologie MeSH
- kolorektální nádory diagnostické zobrazování enzymologie MeSH
- lidé MeSH
- monoklonální protilátky chemie farmakokinetika MeSH
- myši nahé MeSH
- myši MeSH
- pozitronová emisní tomografie MeSH
- radiofarmaka chemie farmakokinetika MeSH
- radioimunodetekce MeSH
- radioizotopy mědi chemie farmakokinetika MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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.
- MeSH
- aktivní transport MeSH
- antigeny nádorové imunologie MeSH
- buňky HT-29 MeSH
- buňky NIH 3T3 MeSH
- imunokonjugáty farmakokinetika farmakologie MeSH
- inhibitory enzymů farmakokinetika farmakologie MeSH
- karboanhydrasa IX antagonisté a inhibitory imunologie MeSH
- kyseliny fosfinové MeSH
- lidé MeSH
- monoklonální protilátky farmakokinetika farmakologie MeSH
- myši nahé MeSH
- myši MeSH
- nádory diagnostické zobrazování enzymologie MeSH
- PET/CT MeSH
- protinádorové látky imunologicky aktivní farmakokinetika farmakologie MeSH
- radiofarmaka farmakokinetika farmakologie MeSH
- radioizotopy mědi farmakokinetika farmakologie MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
