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| Home > Publications database > Done EAZY: An Automated Procedure for 89Zr-Radiolabeling and Size-Exclusion Chromatography Purification of Nanoliposomal Anticancer Therapeutics. |
| Home > Publications database > Done EAZY: An Automated Procedure for 89Zr-Radiolabeling and Size-Exclusion Chromatography Purification of Nanoliposomal Anticancer Therapeutics. |
| Journal Article | DKFZ-2026-01648 |
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2026
American Chemical Society
Washington, DC
Abstract: Liposomal nanomedicines offer a clinically proven platform for enhanced drug delivery, yet their behavior in vivo remains difficult to characterize. Noninvasive positron emission tomography (PET) imaging with radiolabeled liposomes enables quantitative insight into their biodistribution and pharmacokinetics, supporting the rational design and clinical translation of nanocarrier-based therapeutics. Zirconium-89 ([89Zr]Zr) is a positron emitter with a suitable half-life (t1/2 = 78.4 h) for tracking long-circulating nanocarriers such as PEGylated liposomes by PET imaging. However, existing manual labeling protocols often suffer from poor reproducibility, drug leakage, and limited scalability for clinical translation. Automated radiolabeling and purification of macromolecular systems, such as liposomes, antibodies, and antibody fragments, are essential for the reproducible, clinically translatable production of radiopharmaceuticals. However, these requirements necessitate larger and more complex radiosynthesizers that are often not suitable for smaller laboratories. Although automated procedures using complex synthesis modules with integrated high-performance liquid chromatography purification have been demonstrated on larger radiosynthesizers, comparable processes on simpler synthesis platforms remain scarce. To address this gap, this study aimed to develop a fully automated process for the 89Zr-radiolabeling and subsequent size-exclusion chromatography (SEC) purification of doxorubicin-loaded, PEGylated liposomes using the ML Eazy synthesis platform. The process was designed in a GMP-oriented manner with the goal of enabling its future application to other macromolecular radiopharmaceuticals. Using this approach, a fully automated procedure was successfully established on the ML Eazy platform, although optimization of a published labeling method was required to eliminate doxorubicin leakage and improve radiolabeling efficiency. Several system configurations were tested to optimize SEC and sterile filtration, resulting in a robust setup that enabled efficient purification and reproducible performance. Fine-tuning of reagent transfer, gradual pressure increase, and intermediate saline rinsing with subsequent air flushing reduced residual activity in tubing and connectors to <5%. The final automated process achieved consistent radiochemical yields of 67 ± 3% across eight batches prepared under GMP-oriented conditions. Overall, an automated, GMP-oriented all-in-one procedure for 89Zr-labeling with subsequent size-exclusion purification of liposomes has been successfully established, producing sterile-filtered formulations that support future clinical translation. The automated module may also be adapted for other radiolabeling applications using SEC, including antibody labeling.
Keyword(s): ML Eazy ; automation ; liposomes ; nanocarrier ; size-exclusion chromatography ; transmembrane chelation ; zirconium-89
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