E-Poster Presentation 33rd Lorne Cancer Conference 2021

Automated radiosynthesis of [89Zr]Zr-DFOSq-Durvalumab on the iPHASE MultiSyn module (#205)

Christian W Wichmann 1 2 3 4 , Stan Poniger 2 , Nancy Guo 1 , Peter Roselt 5 , Stacey Rudd 4 , Paul S Donnelly 4 , Fiona Hegi-Johnson 5 , Michael MacManus 5 , Andrew M Scott 1 2 3 4
  1. Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia
  2. Austin Health, Heidelberg, VIC, Australia
  3. La Trobe University, Bundoora, VIC, Australia
  4. The University of Melbourne, Parkville, Victoria, Australia
  5. Peter MacCallum Cancer Centre Melbourne, Melbourne, Victoria, Australia

Targeting immune checkpoint proteins such as PD-L1 is changing the landscape of cancer therapy.[1] However, change of PD-L1 expression during chemoradiotherapy has not been well characterised. The Immuno-PET study aims to examine the dynamics of PD-L1 expression via 89Zr-Durvalumab PET imaging before, during and after chemoradiotherapy. To support the large number of clinical productions required for this study, we have developed a fully automated protocol for the radiosynthesis of [89Zr]Zr-DFOSq-Durvalumab.

DFOSq-Durvalumab with an average chelator-to-antibody ratio of 3.69 was used for radiolabelling experiments using an iPHASE MultiSyn module. Reaction kinetics in succinate pH 6 were significantly faster compared to HEPES pH 7.2 with 90% conversion observed in 15 and 60 minutes, respectively. This buffer and pH change also reduced the amount of residual radioactivity in the Zr-89 isotope vial from 24% to 0.5% ± 0.2% (n=5). Addition of 0.02% Tween 80 to the reaction buffer reduced [89Zr]Zr]DFOSq-Durvalumab losses in the reactor from 36% ± 6% (n=4) to 0.2% ± 0.0% (n=2). Interactive peak collection via the PD-10 column radiation profile allowed reproducible collection of the product fraction with low amounts of radioactivity remaining on the PD-10 column (3.0% ± 1.2%, n=3). Residual on the sterile filter was 6.2% ± 1.9% (n=3) and the remaining kit components accounted for 4.3% ± 1.4% (n=3) of radioactivity losses. Typically, 164 MBq of product was formulated in a volume of 2.1 mL with a specific activity of 182 MBq/mg. Radiochemical purity and immunoreactive fraction were always >99% and >93% at end-of-synthesis, respectively, and dropped to 90% and 74% after incubation in human serum for 7 days at 37°C. SEC-HPLC analysis of formulated [89Zr]Zr-DFOSq-Durvalumab showed very good antibody integrity with levels of aggregation at 3.9% ± 0.8% (n=3).

In summary, fully automated production of [89Zr]Zr-DFOSq-Durvalumab for clinical use was achieved using a cassette-based system. The total process yield was improved from 13% to 74.5% ± 5.4% (n=3)  and the procedure was complete within 45 minutes.

  1. Antonia SJ, Villegas A, Daniel D, et al., New England Journal of Medicine 2017, 377 (20), 1919-1929.