Automated radiosynthesis of 89ZrZr-DFOSq-Durvalumab for imaging of PD-L1 expressing tumours in vivo

• Published in: Nuclear medicine and biology 2023-05, Vol.120-121, p.108351
• Main Authors: Wichmann, Christian W, Poniger, Stan, Guo, Nancy, Roselt, Peter, Rudd, Stacey E, Donnelly, Paul S, Blyth, Benjamin, Van Zuylekom, Jessica, Rigopoulos, Angela, Burvenich, Ingrid J G, Morandeau, Laurence, Mohamed, Shifaza, Nowak, Anna K, Hegi-Johnson, Fiona, MacManus, Michael, Scott, Andrew M
• Format: Article
• Language: English
• ISSN: 1872-9614; 1872-9614
• DOI: 10.1016/j.nucmedbio.2023.108351

89Zr-labelled proteins are gaining importance in clinical research in a variety of diseases. To date, no clinical study has been reported that utilizes an automated approach for radiosynthesis of 89Zr-labelled radiopharmaceuticals. We aim to develop an automated method for the clinical production of 89Zr-labelled proteins and apply this method to Durvalumab, a monoclonal antibody targeting PD-L1 immune-checkpoint protein. PD-L1 expression is poorly understood and can be up-regulated over the course of chemo- and radiotherapy treatment. The ImmunoPET multicentre study aims to examine the dynamics of PD-L1 expression via 89Zr-Durvalumab PET imaging before, during, and after chemoradiotherapy. The developed automated technique will enable reproducible clinical production of [89Zr]Zr-DFOSq-Durvalumab for this study at three different sites.OBJECTIVES89Zr-labelled proteins are gaining importance in clinical research in a variety of diseases. To date, no clinical study has been reported that utilizes an automated approach for radiosynthesis of 89Zr-labelled radiopharmaceuticals. We aim to develop an automated method for the clinical production of 89Zr-labelled proteins and apply this method to Durvalumab, a monoclonal antibody targeting PD-L1 immune-checkpoint protein. PD-L1 expression is poorly understood and can be up-regulated over the course of chemo- and radiotherapy treatment. The ImmunoPET multicentre study aims to examine the dynamics of PD-L1 expression via 89Zr-Durvalumab PET imaging before, during, and after chemoradiotherapy. The developed automated technique will enable reproducible clinical production of [89Zr]Zr-DFOSq-Durvalumab for this study at three different sites.Conjugation of Durvalumab to H3DFOSqOEt was optimized for optimal chelator-to-antibody ratio. Automated radiolabelling of H3DFOSq-Durvalumab with zirconium-89 was optimized on the disposable cassette based iPHASE technologies MultiSyn radiosynthesizer using a modified cassette. Activity losses were tracked using a dose calibrator and minimized by optimizing fluid transfers, reaction buffer, antibody formulation additives and pH. The biological profile of the radiolabelled antibody was confirmed in vivo in PD-L1+ (HCC827) and PD-L1- (A549) murine xenografts. Clinical process validation and quality control were performed at three separate study sites to satisfy clinical release criteria.METHODSConjugation of Durvalumab to H3DFOSqOEt was optimized for optimal chelator-to-antibody ratio.