Preparation, Optimisation, and In Vitro Evaluation of [ 18 F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET.

[ 18 F]sodium fluoride ([ 18 F]NaF) is recognised to be superior to [ 99 mTc]-methyl diphosphate ([ 99m Tc]Tc-MDP) and 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) in bone imaging. However, there is concern that [ 18 F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [ 18 F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an N- Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [ 18 F]AlF-NOTA-pamidronic acid was optimised, and it was ensured that all quality control analysis requirements for the radiopharmaceuticals were met prior to the in vitro cell uptake studies. NOTA-pamidronic acid was successfully prepared and radiolabeled with 18 F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl 3 ) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol ( v / v ), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [ 18 F]AlF-NOTA-pamidronic acid was as sensitive as [ 18 F]sodium fluoride ([ 18 F]NaF). Normal human osteoblast cell lines (hFOB 1.19) and human osteosarcoma cell lines (Saos-2) were used for the in vitro cellular uptake studies. It was found that [ 18 F]NaF was higher in both cell lines, but [ 18 F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [ 18 F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.