Development of a Fully Automated FASTlab 2 Process for [¹⁸F]AlF Radiolabelling of NOTA Peptide Conjugates

Aluminium[¹⁸F]fluoride ([¹⁸F]AlF) radiochemistry offers an attractive alternative to conventional radiometals for peptide and protein labelling and has been applied in several clinical radiopharmaceuticals. The method combines the broad availability of [¹⁸F]fluoride with rapid aqueous-phase labelling under mild conditions, making it well suited to biomolecules sensitive to organic solvents or elevated temperatures. To enable routine clinical translation, we developed a fully automated [¹⁸F]AlF radiolabelling process on the GE HealthCare FASTlab 2 synthesis platform using NOTA-AMBA as a model compound. Formulated [¹⁸F]AlF-NOTA-AMBA was produced with a non-decay-corrected radiochemical yield of 63.3% ± 5.0% (n = 3) in a total synthesis time of 20 min. The radioactive concentration at end of synthesis was 831 ± 115 MBq/mL, with a radiochemical purity of 94.1% ± 0.5%. The molar activity was 183.3 ± 20.7 GBq/μmol. No dissociation of [¹⁸F]AlF from the NOTA chelator was observed over 4 h at room temperature, confirming excellent stability. A simple, rapid and fully automated [¹⁸F]AlF labelling method has been established on FASTlab 2. High yields were achieved using low precursor amounts (95 μg, 67.5 nmol) without HPLC purification. The method is readily adaptable to GMP-compliant production of [¹⁸F]AlF-labelled biomolecules for clinical use.