In vitro evaluation of the monoclonal antibody 64Cu-IgG M75 against human carbonic anhydrase IX and its in vivo imaging
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu hodnotící studie, časopisecké články
PubMed
29272822
DOI
10.1016/j.apradiso.2017.12.013
PII: S0969-8043(17)30327-5
Knihovny.cz E-zdroje
- Klíčová slova
- Cu-64, IgG M75, Imaging, Immunoaffinity, Monoclonal antibody,
- 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
- Názvy látek
- antigeny nádorové MeSH
- CA9 protein, human MeSH Prohlížeč
- Copper-64 MeSH Prohlížeč
- imunokonjugáty MeSH
- inhibitory enzymů MeSH
- karboanhydrasa IX MeSH
- kyseliny fosfinové MeSH
- M75 monoclonal antibody MeSH Prohlížeč
- monoklonální protilátky MeSH
- protinádorové látky imunologicky aktivní MeSH
- radiofarmaka MeSH
- radioizotopy mědi 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
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