Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes
Niobium-90 (90Nb) is a positron emitting radionuclide that exhibits attractive characteristics for use in the design and synthesis of radioimmunoconjugates. In the current study we have investigated 90Nb as a possible future isotope for immuno-PET. Prior to 90Nb in vivo studies, this paper describes...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2018
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| _version_ | 1797104209081925632 |
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| author | De La Fuente, A Radchenko, V Tsotakos, T Tsoukalas, C Paravatou-Petsotas, M Harris, AL Köster, U Rösch, F Bouziotis, P |
| author_facet | De La Fuente, A Radchenko, V Tsotakos, T Tsoukalas, C Paravatou-Petsotas, M Harris, AL Köster, U Rösch, F Bouziotis, P |
| author_sort | De La Fuente, A |
| collection | OXFORD |
| description | Niobium-90 (90Nb) is a positron emitting radionuclide that exhibits attractive characteristics for use in the design and synthesis of radioimmunoconjugates. In the current study we have investigated 90Nb as a possible future isotope for immuno-PET. Prior to 90Nb in vivo studies, this paper describes in vitro and ex vivo studies using a Niobium-95 (95Nb)-monoclonal antibody analogue. 95Nb has a half-life of 35 days and is convenient for long-term studies. 95Nb-labelled bevacizumab was evaluated for early antiangiogenic tumor response assessment and the results were compared with other well established PET nuclides for immuno-PET. 95Nb was quantitatively recovered (> 95%) from irradiated natural Zr in a multistep separation. Bevacizumab was modified with the Df-Bz-NCS (Df) chelate and labelled with previously separated 95Nb. Stability of 95Nb-Df-bevacizumab was evaluated in saline and in human plasma over 7 days presenting > 96% and > 94% of intact product, respectively. Biodistribution ex vivo studies were performed on M165 tumor-bearing mice. 95Nb was obtained in high purity (99.999%) and high radioactivity concentration (1.7 MBq/µL) in a total volume of 200 µL oxalic acid (0.1 M), ready for labelling. Df-bevacizumab labelling was efficient (> 95%) and in vitro stability of 95Nb-Df-bevacizumab was high. Ex vivo studies displayed good tumor-to-background ratios, optimum after 2 days p.i., after iv injection of 20 µg of antibody per mouse. 95Nb was successfully produced and purified from the irradiated target. Labeling of bevacizumab pre-modified with desferrioxamine was achieved in high yields. After in vitro stability of 95Nb-Df-bevacizumab was demonstrated, ex vivo biodistribution studies showed specific tumor uptake in M165 tumor-bearing mice. Consequently, in vivo studies with 90Nb-Df-bevacizumab and small animal PET are in preparation, and we expect that 90Nb-Df-conjugated antibodies will show potential for immuno-PET. |
| first_indexed | 2024-03-07T06:30:38Z |
| format | Journal article |
| id | oxford-uuid:f5df0777-d044-4daa-a022-4acbcd017bf0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:30:38Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:f5df0777-d044-4daa-a022-4acbcd017bf02022-03-27T12:30:37ZConjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f5df0777-d044-4daa-a022-4acbcd017bf0EnglishSymplectic Elements at OxfordSpringer Nature2018De La Fuente, ARadchenko, VTsotakos, TTsoukalas, CParavatou-Petsotas, MHarris, ALKöster, URösch, FBouziotis, PNiobium-90 (90Nb) is a positron emitting radionuclide that exhibits attractive characteristics for use in the design and synthesis of radioimmunoconjugates. In the current study we have investigated 90Nb as a possible future isotope for immuno-PET. Prior to 90Nb in vivo studies, this paper describes in vitro and ex vivo studies using a Niobium-95 (95Nb)-monoclonal antibody analogue. 95Nb has a half-life of 35 days and is convenient for long-term studies. 95Nb-labelled bevacizumab was evaluated for early antiangiogenic tumor response assessment and the results were compared with other well established PET nuclides for immuno-PET. 95Nb was quantitatively recovered (> 95%) from irradiated natural Zr in a multistep separation. Bevacizumab was modified with the Df-Bz-NCS (Df) chelate and labelled with previously separated 95Nb. Stability of 95Nb-Df-bevacizumab was evaluated in saline and in human plasma over 7 days presenting > 96% and > 94% of intact product, respectively. Biodistribution ex vivo studies were performed on M165 tumor-bearing mice. 95Nb was obtained in high purity (99.999%) and high radioactivity concentration (1.7 MBq/µL) in a total volume of 200 µL oxalic acid (0.1 M), ready for labelling. Df-bevacizumab labelling was efficient (> 95%) and in vitro stability of 95Nb-Df-bevacizumab was high. Ex vivo studies displayed good tumor-to-background ratios, optimum after 2 days p.i., after iv injection of 20 µg of antibody per mouse. 95Nb was successfully produced and purified from the irradiated target. Labeling of bevacizumab pre-modified with desferrioxamine was achieved in high yields. After in vitro stability of 95Nb-Df-bevacizumab was demonstrated, ex vivo biodistribution studies showed specific tumor uptake in M165 tumor-bearing mice. Consequently, in vivo studies with 90Nb-Df-bevacizumab and small animal PET are in preparation, and we expect that 90Nb-Df-conjugated antibodies will show potential for immuno-PET. |
| spellingShingle | De La Fuente, A Radchenko, V Tsotakos, T Tsoukalas, C Paravatou-Petsotas, M Harris, AL Köster, U Rösch, F Bouziotis, P Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes |
| title | Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes |
| title_full | Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes |
| title_fullStr | Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes |
| title_full_unstemmed | Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes |
| title_short | Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes |
| title_sort | conjugation labelling and in vitro in vivo assessment of an anti vegf monoclonal antibody labelled with niobium isotopes |
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