@article {delaFuente2018, title = {Conjugation, labelling and in vitro/in vivo assessment of an anti-VEGF monoclonal antibody labelled with niobium isotopes}, journal = {Journal of Radioanalytical and Nuclear Chemistry}, volume = {318}, number = {3}, year = {2018}, month = {Dec}, pages = {1991{\textendash}1997}, abstract = {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 (>{\th}inspace}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 >{\th}inspace}96{\%} and >{\th}inspace}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/{\textmu}L) in a total volume of 200~{\textmu}L oxalic acid (0.1~M), ready for labelling. Df-bevacizumab labelling was efficient (>{\th}inspace}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~{\textmu}g 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.}, issn = {1588-2780}, doi = {10.1007/s10967-018-6314-2}, url = {https://doi.org/10.1007/s10967-018-6314-2}, author = {de la Fuente, A. and Radchenko, V. and Tsotakos, T. and Tsoukalas, C. and Paravatou-Petsotas, M. and Harris, A. L. and K{\"o}ster, U. and R{\"o}sch, F. and Bouziotis, P.} }