In four automated production runs, the system delivered the final radiopharmaceutical with 100% radiochemical purity by high-performance liquid chromatography and 99–100% purity by thin-layer chromatography, according to a study published in Frontiers in Nuclear Medicine.
The resulting [89Zr]Zr(C2O4)2 was used to radiolabel DFO-conjugated trastuzumab, followed by PD-10 size-exclusion purification. Immuno-PET with long-lived positron emitters, such as [89Zr]zirconium, enables whole-body visualization and quantification of HER2 expression. The clinical rationale is that HER2-positive breast cancer is an aggressive subtype in which accurate, non-invasive assessment of HER2 expression is important for patient stratification and therapy monitoring.
The automated workflow integrated target dissolution, [89Zr]zirconium capture and elution, buffer adjustment, antibody radiolabeling, PD-10 purification and sterile filtration within a single disposable cassette installed on an ALLinOne synthesis module.
Target dissolution and SPE purification provided approximately 90% recovery of [89Zr]Zr(C2O4)2 with high radionuclidic purity.
Preliminary manual experiments achieved radiolabeling yields of approximately 90% after 60 minutes.
The four automated production runs used starting activities ranging from 37 to 185 MBq and produced isolated radiochemical yields of 65–78%. The automated isolated radiochemical yields of 65–78% were lower than the approximately 90% yields obtained in the preliminary manual experiments; the authors indicate that the main opportunity for further optimization lies in overall activity recovery and fluidic transfer efficiency rather than in the chemical purity of the final product.
HPLC showed 100% radiochemical purity in every automated production, while thin-layer chromatography demonstrated 99–100% purity. After PD-10 purification, the final product showed 99–100% radiochemical purity by TLC and a pH of approximately 7.
The authors conclude that the cassette-based system successfully integrated zirconium-89 production and purification with automated radiolabeling and purification of DFO-trastuzumab in a single sequence. The authors state that the system reduces direct operator handling of radioactive material and provides a standardized platform that may be further developed into a Good Manufacturing Practice–compliant production method for [89Zr]-labeled monoclonal antibodies.
Subject of Research: An automated cassette-based process for producing, purifying and radiolabeling the zirconium-89-labeled antibody trastuzumab for HER2 immuno-PET imaging.
Article Title: Automated cassette-based production, purification, and radiolabeling of [89Zr]Zr-DFO-trastuzumab
Article References: Tesse, G., Capasso, G., Cazzola, E., Tolomeo, A., Altamura, C., Cileo, S. I., Lovino, V., Brattoli, S., Casilli, R., Riglietti, A., Gorgoni, G., Malachini, M., Cisternino, S., Stefanucci, A., & Dimiccoli, V. (2026). Automated cassette-based production, purification, and radiolabeling of [89Zr]Zr-DFO-trastuzumab. Frontiers in Nuclear Medicine, 6, Article 1942773. https://doi.org/10.3389/fnume.2026.1942773
Image Credits: AI Generated
DOI: 10.3389/fnume.2026.1942773
Keywords: zirconium-89, trastuzumab, immuno-PET, radiopharmaceuticals, HER2-positive breast cancer, radiochemistry, automation, solid-phase extraction, radiochemical purity, GMP, Automated, cassette-based
