Diagnostic HER2-binding radiopharmaceutical, [⁶⁸Ga]Ga-ABY-025, for routine clinical use in breast cancer patients

[⁶⁸Ga]Ga-ABY-025/PET-CT targeting human epidermal growth factor receptor type 2 (HER2) has demonstrated its potential clinical value for the detection and quantification of HER2 in a phase I clinical study with breast cancer patients. Previously, the radiopharmaceutical was prepared manually, however larger scale of multicenter clinical trials and routine healthcare requires automation of the production process to limit the operator radiation dose, improve tracer manufacturing robustness, and provide on-line documentation for good manufacturing practice (GMP) compliance. The production of [⁶⁸Ga]Ga-ABY-025 was implemented on the Modular-Lab PharmTrace synthesis platform (Eckert & Ziegler) and disposable cassettes were developed. Pharmaceutical grade ⁶⁸Ge/⁶⁸Ga generator (GalliaPharm^®) was used in the study. The active pharmaceutical ingredient starting material ABY-025 (GMP grade) was provided by Affibody AB. The patient examinations were conducted using a Discovery MI PET/CT scanner (20 cm FOV, GE Healthcare). Reproducible and GMP compliant fully automated production of [⁶⁸Ga]Ga-ABY-025 was developed. The radiochemical purity of the product was 98.7 ± 0.6% with total peptide content of 315 ± 15 µg (n = 3). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity were controlled and met acceptance criteria. The product was stable at ambient temperature for at least 2 h. The primary tumor and metastasis were detected with SUV_max values of 8.3 and 16.0, respectively. Automated production of [⁶⁸Ga]Ga-ABY-025 was established and the process was validated enabling standardized multicenter phase II and III clinical trials and routine clinical use. Patient examinations conformed to the radiopharmaceutical biodistribution observed in the previous phase I study.