• 1 Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia
  • 2 Department of Pharmacy Practice, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Malaysia
  • 3 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
  • 4 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
  • 5 Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia
  • 6 Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia
Molecules, 2022 Nov 17;27(22).
PMID: 36432069 DOI: 10.3390/molecules27227969


[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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.