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

[<sup>18</sup>F]sodium fluoride ([<sup>18</sup>F]NaF) is recognised to be superior to [<sup>99</sup>mTc]-methyl diphosphate ([<sup>99m</sup>Tc]Tc-MDP) and <i>2-deoxy-2-[<sup>18</sup>F]fluoro-D-glucose</i> ([<sup>18</sup...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/22/7969
_version_ 1827644003603972096
author 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
author_facet 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
author_sort Hishar Hassan
collection DOAJ
description [<sup>18</sup>F]sodium fluoride ([<sup>18</sup>F]NaF) is recognised to be superior to [<sup>99</sup>mTc]-methyl diphosphate ([<sup>99m</sup>Tc]Tc-MDP) and <i>2-deoxy-2-[<sup>18</sup>F]fluoro-D-glucose</i> ([<sup>18</sup>F]FDG) in bone imaging. However, there is concern that [<sup>18</sup>F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [<sup>18</sup>F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an <i>N-</i>Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [<sup>18</sup>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</sup>F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl<sub>3</sub>) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol (<i>v</i>/<i>v</i>), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [<sup>18</sup>F]AlF-NOTA-pamidronic acid was as sensitive as [<sup>18</sup>F]sodium fluoride ([<sup>18</sup>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</sup>F]NaF was higher in both cell lines, but [<sup>18</sup>F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [<sup>18</sup>F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.
first_indexed 2024-03-09T18:06:57Z
format Article
id doaj.art-6c964b3777914e289d2f231908c13778
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-09T18:06:57Z
publishDate 2022-11-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-6c964b3777914e289d2f231908c137782023-11-24T09:24:13ZengMDPI AGMolecules1420-30492022-11-012722796910.3390/molecules27227969Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PETHishar Hassan0Muhamad Faiz Othman1Hairil Rashmizal Abdul Razak2Zainul Amiruddin Zakaria3Fathinul Fikri Ahmad Saad4Mohd Azuraidi Osman5Loh Hui Yi6Zarif Ashhar7Jaleezah Idris8Mohd Hamdi Noor Abdul Hamid9Zaitulhusna M. Safee10Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia (UPM), Serdang 43400, MalaysiaDepartment of Pharmacy Practice, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, MalaysiaMedical Imaging Program, Department of Health and Care Professions, Faculty of Health and Life Sciences, St Luke’s Campus, University of Exeter, Devon EX1 2LU, UKBorneo Research on Algesia, Inflammation and Neurodegeneration (BRAIN) Group, Department of Biomedicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, MalaysiaCentre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia (UPM), Serdang 43400, MalaysiaDepartment of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, MalaysiaDepartment of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, MalaysiaDepartment of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, MalaysiaDepartment of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, MalaysiaDepartment of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, MalaysiaDepartment of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia[<sup>18</sup>F]sodium fluoride ([<sup>18</sup>F]NaF) is recognised to be superior to [<sup>99</sup>mTc]-methyl diphosphate ([<sup>99m</sup>Tc]Tc-MDP) and <i>2-deoxy-2-[<sup>18</sup>F]fluoro-D-glucose</i> ([<sup>18</sup>F]FDG) in bone imaging. However, there is concern that [<sup>18</sup>F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [<sup>18</sup>F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an <i>N-</i>Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [<sup>18</sup>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</sup>F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl<sub>3</sub>) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol (<i>v</i>/<i>v</i>), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [<sup>18</sup>F]AlF-NOTA-pamidronic acid was as sensitive as [<sup>18</sup>F]sodium fluoride ([<sup>18</sup>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</sup>F]NaF was higher in both cell lines, but [<sup>18</sup>F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [<sup>18</sup>F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.https://www.mdpi.com/1420-3049/27/22/7969<sup>18</sup>Faluminium fluoride (Al-F)pamidronic acidradiopharmaceuticalsradiochemistrypositron emission tomography
spellingShingle 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
Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
Molecules
<sup>18</sup>F
aluminium fluoride (Al-F)
pamidronic acid
radiopharmaceuticals
radiochemistry
positron emission tomography
title Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
title_full Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
title_fullStr Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
title_full_unstemmed Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
title_short Preparation, Optimisation, and In Vitro Evaluation of [<sup>18</sup>F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET
title_sort preparation optimisation and in vitro evaluation of sup 18 sup f alf nota pamidronic acid for bone imaging pet
topic <sup>18</sup>F
aluminium fluoride (Al-F)
pamidronic acid
radiopharmaceuticals
radiochemistry
positron emission tomography
url https://www.mdpi.com/1420-3049/27/22/7969
work_keys_str_mv AT hisharhassan preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT muhamadfaizothman preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT hairilrashmizalabdulrazak preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT zainulamiruddinzakaria preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT fathinulfikriahmadsaad preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT mohdazuraidiosman preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT lohhuiyi preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT zarifashhar preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT jaleezahidris preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT mohdhamdinoorabdulhamid preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet
AT zaitulhusnamsafee preparationoptimisationandinvitroevaluationofsup18supfalfnotapamidronicacidforboneimagingpet