A translational journey in Germany: From literature to local implementation of [89Zr]Zr-DFO-trastuzumab

Abstract [⁸⁹Zr]Zr-DFO-trastuzumab has emerged as a powerful tool to visualise non-invasively HER2 expression across metastatic lesions, complementing conventional pathological HER2 evaluation and helping to identify patients unlikely to benefit from therapy with trastuzumab-based therapies. This paper outlines the roadmap of the manufacturing implementation of [89Zr]Zr-DFO-trastuzumab at our centre in Germany. In this paper, we describe the key questions encountered during implementation of the manufacturing process for [89Zr]Zr-DFO-trastuzumab and how these were addressed through discussions between academia, hospital departments, teams experienced in the radiolabelling of antibodies and regulatory authorities. Discussions with multiple institutions were essential for the implementation of the GMP-compliant radiosynthesis of [⁸⁹Zr]Zr-DFO-trastuzumab at our manufacturing site. Example decisions included shortening the shelf-life of [⁸⁹Zr]Zr-DFO-trastuzumab to 24 hours to mitigate container-closure integrity concerns and adoption of a bead-based method to determine the immunoreactive fraction. This work presents a practical overview of operational considerations relevant to the clinical implementation of [⁸⁹Zr]Zr-DFO-trastuzumab, with potential applicability to other ⁸⁹Zr-labelled high-molecular-weight radiotracers in Germany. By sharing these practical insights, we aim to support broader patient access to established radiopharmaceuticals and encourage dialogue around open regulatory and practical questions, particularly in anticipation of future clinical trials.