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In vitro evaluation of the monoclonal antibody 64 Cu-IgG M75 against human carbonic anhydrase IX and its in vivo imaging.
- Source :
-
Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine [Appl Radiat Isot] 2018 Mar; Vol. 133, pp. 9-13. Date of Electronic Publication: 2017 Dec 16. - Publication Year :
- 2018
-
Abstract
- 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 <superscript>64</superscript> Cu (T <subscript>½</subscript> = 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 <superscript>64</superscript> Cu. 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 K <subscript>D</subscript> 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 <superscript>64</superscript> Cu-PS-IgG M75 seems to be a suitable candidate for PET diagnostics of hypoxic tumours expressing human carbonic anhydrase IX.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal pharmacokinetics
Antineoplastic Agents, Immunological pharmacokinetics
Biological Transport, Active
Copper Radioisotopes pharmacokinetics
Enzyme Inhibitors pharmacokinetics
Enzyme Inhibitors pharmacology
HT29 Cells
Humans
Immunoconjugates pharmacokinetics
Immunoconjugates pharmacology
In Vitro Techniques
Mice
Mice, Nude
NIH 3T3 Cells
Neoplasms diagnostic imaging
Neoplasms enzymology
Phosphinic Acids
Positron Emission Tomography Computed Tomography
Radiopharmaceuticals pharmacokinetics
Antibodies, Monoclonal pharmacology
Antigens, Neoplasm immunology
Antineoplastic Agents, Immunological pharmacology
Carbonic Anhydrase IX antagonists & inhibitors
Carbonic Anhydrase IX immunology
Copper Radioisotopes pharmacology
Radiopharmaceuticals pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9800
- Volume :
- 133
- Database :
- MEDLINE
- Journal :
- Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine
- Publication Type :
- Academic Journal
- Accession number :
- 29272822
- Full Text :
- https://doi.org/10.1016/j.apradiso.2017.12.013