Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
Hishar Hassan,
Muhamad Faiz Othman,
Hairil Rashmizal Abdul Razak,
Zainul Amiruddin Zakaria,
Fathinul Fikri Ahmad Saad,
Mohd Azuraidi Osman,
Loh Hui Yi,
Zarif Ashhar,
Jaleezah Idris,
Mohd Hamdi Noor Abdul Hamid,
Zaitulhusna M. Safee
Affiliations
Hishar Hassan
Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia
Muhamad Faiz Othman
Department of Pharmacy Practice, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Malaysia
Hairil Rashmizal Abdul Razak
Medical Imaging Program, Department of Health and Care Professions, Faculty of Health and Life Sciences, St Luke’s Campus, University of Exeter, Devon EX1 2LU, UK
Zainul Amiruddin Zakaria
Borneo Research on Algesia, Inflammation and Neurodegeneration (BRAIN) Group, Department of Biomedicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia
Fathinul Fikri Ahmad Saad
Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia
Mohd Azuraidi Osman
Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia
Loh Hui Yi
Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia
Zarif Ashhar
Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia
Jaleezah Idris
Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia
Mohd Hamdi Noor Abdul Hamid
Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia
Zaitulhusna M. Safee
Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia
[18F]sodium fluoride ([18F]NaF) is recognised to be superior to [99mTc]-methyl diphosphate ([99mTc]Tc-MDP) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in bone imaging. However, there is concern that [18F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [18F]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 [18F]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 18F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl3) 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 [18F]AlF-NOTA-pamidronic acid was as sensitive as [18F]sodium fluoride ([18F]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 [18F]NaF was higher in both cell lines, but [18F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [18F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.
