Development of a Fully Automated FASTlab 2 Process for 18 FAlF Radiolabelling of NOTA Peptide Conjugates

Aluminium18Ffluoride (18FAlF) 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 18Ffluoride 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 18FAlF radiolabelling process on the GE HealthCare FASTlab 2 synthesis platform using NOTA-AMBA as a model compound. Formulated 18FAlF-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 18FAlF from the NOTA chelator was observed over 4 h at room temperature, confirming excellent stability. A simple, rapid and fully automated 18FAlF 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 18FAlF-labelled biomolecules for clinical use.