Preparation and testing of bevacizumab radioimmunoconjugates with Bismuth-213 and Bismuth-205/Bismuth-206

Cancer Biology & Therapy
S M Abbas RizviBarry J Allen

Abstract

Bevacizumab, a humanized anti-VEGF monoclonal antibody has shown promise in various clinical trials. We report the development and testing of Bi-213 (an alpha-emitting radionuclide) labeled bevacizumab for in vitro and in vivo studies using two different chelators viz cDTPA and CHX-A''. The developed labeling method showed high labeling yields of 93.6% and 89.7% for cDTPA and CHX-A'' respectively and the results were reproducible. The in vitro and in vivo stability tests were carried out using Bi-213 and long half-life Bismuth isotope (Bi-205/Bi-206) for pharmacokinetics. The in vitro results showed remarkable stability of the radiolabeled bevacizumab regardless of the chelator. The in vivo pharmacokinetics studies however, showed that the uptake and retention of cDTPA-bevacizumab was significantly higher in kidneys (p-value 0.02) and lower in liver and spleen (p-value <0.0001 and 0.0009 respectively). The values for the two conjugates compared well in blood but the longer term data for CHX-A'' conjugate showed slow clearance resulting in a significantly longer blood half-life of the product (211 hours compared to 4 hours for cDTPA-bevacizumab). Preliminary in vivo results showed increased efficacy of the combination therapy co...Continue Reading

Citations

Dec 7, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Young-Seung Kim, Martin W Brechbiel
Nov 9, 2011·Nature Reviews. Clinical Oncology·Jean-Pierre PougetDavid Azria
May 4, 2013·Immunotherapy·Isabelle Navarro-TeulonJean-Pierre Pouget
Nov 6, 2013·Immunotherapy·Raymond A Clarke, Barry J Allen
Jul 24, 2014·AJR. American Journal of Roentgenology·Thaddeus J WadasAkiva Mintz
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Alireza Khorami-MoghadamBehrouz Alirezapour
Jun 9, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·G MontavonA Morgenstern
Nov 1, 2018·Chemical Reviews·Thomas I Kostelnik, Chris Orvig
May 8, 2018·Molecular Pharmaceutics·Ryan YudistiroYoshito Tsushima

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