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

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 22
• Main Authors: Hassan, Hishar, Othman, Muhamad Faiz, Abdul Razak, Hairil Rashmizal, Zakaria, Zainul Amiruddin, Ahmad Saad, Fathinul Fikri, Osman, Mohd Azuraidi, Yi, Loh Hui, Ashhar, Zarif, Idris, Jaleezah, Abdul Hamid, Mohd Hamdi Noor, Safee, Zaitulhusna M
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.11.2022
• Subjects: Aluminum compounds; Medical research; Medicine, Experimental; Zoledronic acid; Massachusetts; Malaysia
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27227969

[[sup.18]F]sodium fluoride ([[sup.18]F]NaF) is recognised to be superior to [[sup.99]mTc]-methyl diphosphate ([[sup.99m]Tc]Tc-MDP) and 2-deoxy-2-[18F]fluoro-D-glucose ([[sup.18]F]FDG) in bone imaging. However, there is concern that [[sup.18]F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [[sup.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 [[sup.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 [sup.18]F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl[sub.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 [[sup.18]F]AlF-NOTA-pamidronic acid was as sensitive as [[sup.18]F]sodium fluoride ([[sup.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 [[sup.18]F]NaF was higher in both cell lines, but [[sup.18]F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [[sup.18]F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.