{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:06:02Z","timestamp":1768349162667,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universiti Putra Malaysia","award":["9580700"],"award-info":[{"award-number":["9580700"]}]},{"name":"Universiti Putra Malaysia","award":["600-RMC\/GPM LPHD 5\/3 (129\/2021)"],"award-info":[{"award-number":["600-RMC\/GPM LPHD 5\/3 (129\/2021)"]}]},{"name":"Universiti Teknologi MARA","award":["9580700"],"award-info":[{"award-number":["9580700"]}]},{"name":"Universiti Teknologi MARA","award":["600-RMC\/GPM LPHD 5\/3 (129\/2021)"],"award-info":[{"award-number":["600-RMC\/GPM LPHD 5\/3 (129\/2021)"]}]},{"name":"the Ministry of Higher Education, Malaysia (Hadiah Latihan Persekutuan\u2014SLPP)","award":["9580700"],"award-info":[{"award-number":["9580700"]}]},{"name":"the Ministry of Higher Education, Malaysia (Hadiah Latihan Persekutuan\u2014SLPP)","award":["600-RMC\/GPM LPHD 5\/3 (129\/2021)"],"award-info":[{"award-number":["600-RMC\/GPM LPHD 5\/3 (129\/2021)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>[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 \u00b0C 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.<\/jats:p>","DOI":"10.3390\/molecules27227969","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T06:11:34Z","timestamp":1668751894000},"page":"7969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preparation, Optimisation, and In Vitro Evaluation of [18F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-8063","authenticated-orcid":false,"given":"Hishar","family":"Hassan","sequence":"first","affiliation":[{"name":"Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9024-4548","authenticated-orcid":false,"given":"Muhamad Faiz","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8266-0381","authenticated-orcid":false,"given":"Hairil Rashmizal","family":"Abdul Razak","sequence":"additional","affiliation":[{"name":"Medical Imaging Program, Department of Health and Care Professions, Faculty of Health and Life Sciences, St Luke\u2019s Campus, University of Exeter, Devon EX1 2LU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5525-7821","authenticated-orcid":false,"given":"Zainul Amiruddin","family":"Zakaria","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0499-7747","authenticated-orcid":false,"given":"Fathinul Fikri","family":"Ahmad Saad","sequence":"additional","affiliation":[{"name":"Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Azuraidi","family":"Osman","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loh Hui","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-4705","authenticated-orcid":false,"given":"Zarif","family":"Ashhar","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaleezah","family":"Idris","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Hamdi Noor","family":"Abdul Hamid","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaitulhusna M.","family":"Safee","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, National Cancer Institute, Putrajaya 62250, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","unstructured":"Pullan, J.E., and Lotfollahzadeh, S. (2022). Primary Bone Cancer, StatPearls Publishing."},{"key":"ref_2","first-page":"1099","article-title":"Biology and pathogenesis of human osteosarcoma (Review)","volume":"19","author":"Fernandes","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1155\/2016\/3631764","article-title":"Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies","volume":"2016","author":"Abarrategi","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_4","unstructured":"(2022, July 25). Cancer Research UK Survival for Bone Cancer. Available online: https:\/\/www.cancerresearchuk.org\/about-cancer\/bone-cancer\/survival."},{"key":"ref_5","unstructured":"(2022, July 18). The American Cancer Society Survival Rates for Osteosarcoma. Available online: https:\/\/www.cancer.org\/cancer\/osteosarcoma\/detection-diagnosis-staging\/survival-rates.html."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9840962","DOI":"10.1155\/2018\/9840962","article-title":"Prostate Osteoblast-Like Cells: A Reliable Prognostic Marker of Bone Metastasis in Prostate Cancer Patients","volume":"2018","author":"Scimeca","year":"2018","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1002\/ijc.26024","article-title":"Steps in prostate cancer progression that lead to bone metastasis","volume":"128","author":"Jin","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1210\/js.2018-00425","article-title":"Mechanisms of osteoblastic bone metastasis in prostate cancer: Role of prostatic acid phosphatase","volume":"3","author":"Izadmehr","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_9","first-page":"63","article-title":"V Dosimetry and toxicity of samarium-153-EDTMP administered for bone pain due to skeletal metastases","volume":"35","author":"Bayouth","year":"1994","journal-title":"J. Nucl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cpet.2010.04.001","article-title":"FDG PET for the detection of bone metastases: Sensitivity, specificity and comparison with other imaging modalities","volume":"5","author":"Costelloe","year":"2010","journal-title":"PET Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.crad.2016.01.026","article-title":"Multi-technique imaging of bone metastases: Spotlight on PET-CT","volume":"71","author":"Azad","year":"2016","journal-title":"Clin. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/wjnm.WJNM_54_17","article-title":"Nuclear Medicine in Prostate Cancer: A New Era for Radiotracers","volume":"17","author":"Cuccurullo","year":"2018","journal-title":"World J. Nucl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1007\/s13277-013-1218-9","article-title":"High-level expression of CXCR4 in breast cancer is associated with early distant and bone metastases","volume":"35","author":"Hung","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2967\/jnumed.117.196444","article-title":"The Utility of PET\/CT in the Planning of External Radiation Therapy for Prostate Cancer","volume":"59","author":"Calais","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jbo.2015.08.002","article-title":"The role of 18F-NaF PET\/CT in metastatic bone disease","volume":"4","author":"Araz","year":"2015","journal-title":"J. Bone Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"320","DOI":"10.2967\/jnumed.117.193854","article-title":"(68)Ga-Pentixafor PET\/CT Imaging of Chemokine Receptor CXCR4 in Chronic Infection of the Bone: First Insights","volume":"59","author":"Bouter","year":"2018","journal-title":"J. Nucl. Med."},{"key":"ref_17","first-page":"1623","article-title":"Sensitivity in Detecting Osseous Lesions Depends on Anatomic Localization: Planar Bone Scintigraphy Versus 18F PET","volume":"40","author":"Schirrmeister","year":"1999","journal-title":"J. Nucl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1200\/JCO.1999.17.8.2381","article-title":"Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography","volume":"17","author":"Schirrmeister","year":"1999","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_19","first-page":"1295","article-title":"Newer PET application with an old tracer: Role of 18F-NaF skeletal PET\/CT in oncologic practice","volume":"34","author":"Bastawrous","year":"2014","journal-title":"Radio Graph."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/212901a0","article-title":"Effect of Pyrophosphate on Hydroxyapatite and Its Implications in Calcium Homeostasis","volume":"212","author":"Fleisch","year":"1966","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00198-007-0540-8","article-title":"Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy","volume":"19","author":"Russell","year":"2008","journal-title":"Osteoporos. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1038\/s41598-021-85073-0","article-title":"Effects of administration route on uptake kinetics of 18F-sodium fluoride positron emission tomography in mice","volume":"11","author":"Tavares","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1021\/acs.bioconjchem.0c00401","article-title":"[68 Ga]Ga-THP-Pam: A Bisphosphonate PET Tracer with Facile Radiolabeling and Broad Calcium Mineral Affinity","volume":"32","author":"Keeling","year":"2020","journal-title":"Bioconjug. Chem."},{"key":"ref_24","first-page":"S259","article-title":"A computational model delineates differences in hydroxyapatite binding affinities of bisphosphonates in clinical use VO\u201420 RT\u2014Conference Proceedings","volume":"20","author":"Ebetino","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/cmdc.201000016","article-title":"An in vitro assay to measure targeted drug delivery to bone mineral","volume":"5","author":"Jahnke","year":"2010","journal-title":"ChemMedChem"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/cmmi.1606","article-title":"Gallium(III) complexes of NOTA-bis (phosphonate) conjugates as PET radiotracers for bone imaging","volume":"10","author":"Holub","year":"2015","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s41181-016-0017-1","article-title":"Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid","volume":"1","author":"Meckel","year":"2016","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00259-016-3469-3","article-title":"Evaluation of bone-seeking novel radiotracer (68)Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast","volume":"44","author":"Passah","year":"2017","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_29","first-page":"1059","article-title":"The Shortage of Approved 68Ge\/68Ga Generators\u2014Incoming Material Inspection and GMP Compliant Use of Non-Approved Generators","volume":"60","author":"Mueller","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kang, D., Simon, U., Mottaghy, F.M., and Vogg, A.T.J. (2021). Labelling via [al18f]2+ using precomplexed al-noda moieties. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080818"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"991","DOI":"10.2967\/jnumed.108.060418","article-title":"A novel method of 18F radiolabeling for PET","volume":"50","author":"McBride","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15389","DOI":"10.1039\/C9NJ00722A","article-title":"Direct radiofluorination of heat-sensitive antibody by Al-18F complexation","volume":"43","author":"Huynh","year":"2019","journal-title":"New J. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20536","DOI":"10.3390\/molecules191220536","article-title":"18 F-labeled peptides: The future is bright","volume":"19","author":"Richter","year":"2014","journal-title":"Molecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s41181-021-00141-0","article-title":"The aluminium-[18F] fluoride revolution: Simple radiochemistry with a big impact for radiolabelled biomolecules","volume":"6","author":"Archibald","year":"2021","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.18383\/j.tom.2016.00130","article-title":"First 18 F-Labeled Pentixafor-Based Imaging Agent for PET Imaging of CXCR4 Expression In Vivo","volume":"2","author":"Poschenrieder","year":"2016","journal-title":"Tomography"},{"key":"ref_36","unstructured":"(2020, November 23). ThermoFisher Scientific Amine-reactive Crosslinker Chemistry. Available online: https:\/\/www.thermofisher.com.my\/en\/home\/life-science\/protein-biology\/protein-biology-learning-center\/protein-biology-resource-library\/pierce-protein-methods\/amine-reactive-crosslinker-chemistry.html."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/B978-0-12-382239-0.00003-0","article-title":"The Reactions of Bioconjugation","volume":"2013","author":"Hermanson","year":"2013","journal-title":"Bioconjugate Tech."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.nucmedbio.2018.10.003","article-title":"Al18F-complexation of DFH17, a NOTA-conjugated adrenomedullin analog, for PET imaging of pulmonary circulation","volume":"67","author":"Harel","year":"2018","journal-title":"Nucl. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hermanson, G.T. (2013). The Reactions of Bioconjugation. Bioconjugate Techniques, Academic Press.","DOI":"10.1016\/B978-0-12-382239-0.00003-0"},{"key":"ref_40","unstructured":"Woodman, R.H. (2021, September 01). Bioconjugation Discussion Reasons for Choosing NHS, TFP, or PFP Esters for Conjugating to Amines. Available online: https:\/\/www.researchgate.net\/post\/Bioconjugation_Discussion_Reasons_for_Choosing_NHS_TFP_or_PFP_esters_for_conjugating_to_amines."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5665","DOI":"10.1021\/acs.analchem.7b00096","article-title":"Think Negative: Finding the Best Electrospray Ionization\/MS Mode for Your Analyte","volume":"89","author":"Liigand","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_42","unstructured":"Strupat, K., Scheibner, O., and Bromirski, M. (2013). High-resolution, accurate-mass Orbitrap Mass Spectrometry\u2014Definitions, opportunities, and advantages. Tech. Note 64287, 1\u20135."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ijms.2010.07.017","article-title":"Fragmentation pathways of eight nitrogen-containing bisphosphonates (BPs) investigated by ESI-MSn in negative ion mode","volume":"295","author":"Qu","year":"2010","journal-title":"Int. J. Mass Spectrom."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/1098-2787(2000)19:6<398::AID-MAS3>3.0.CO;2-B","article-title":"Applications and mechanisms of charge-remote fragmentation","volume":"19","author":"Cheng","year":"2000","journal-title":"Mass Spectrom. Rev."},{"key":"ref_45","unstructured":"International Atomic Energy Agency (2012). Cyclotron Produced Radionuclides: Operation and Maintenance of Gas and Liquid Targets, International Atomic Energy Agency (IAEA)."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/jlcr.3161","article-title":"Al18F labeling of peptides and proteins","volume":"57","author":"Laverman","year":"2014","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1021\/acs.bioconjchem.6b00012","article-title":"New Chelators for Low Temperature Al18F-Labeling of Biomolecules","volume":"27","author":"Cleeren","year":"2016","journal-title":"Bioconjug. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"49586","DOI":"10.1039\/C7RA09076E","article-title":"Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling","volume":"7","author":"Tsionou","year":"2017","journal-title":"RSC Adv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.tibtech.2014.03.001","article-title":"Nanobody-based products as research and diagnostic tools","volume":"32","author":"Muyldermans","year":"2014","journal-title":"Trends Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1515\/ract-2021-1024","article-title":"Optimal 18F-fluorination conditions for the high radiochemical yield of [18F]AlF-NOTA-NHS complexes","volume":"109","author":"Hassan","year":"2021","journal-title":"Radiochim. Acta"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/2191-219X-3-36","article-title":"Radiofluorination using aluminum-fluoride (Al18F)","volume":"3","author":"McBride","year":"2013","journal-title":"EJNMMI Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1021\/bc200175c","article-title":"High-yielding aqueous 18F-labeling of peptides via Al 18F chelation","volume":"22","author":"McBride","year":"2011","journal-title":"Bioconjug. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1021\/bc100137x","article-title":"Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex","volume":"21","author":"McBride","year":"2010","journal-title":"Bioconjug. Chem."},{"key":"ref_54","first-page":"59","article-title":"Head-to-head Comparison of the 18F-AlF-NOTA-Octreotide and 68Ga-DOTATATE PET\/CT within patients with Neuroendocrine Neoplasms","volume":"61","author":"Hou","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s41181-018-0039-y","article-title":"Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform","volume":"3","author":"Giglio","year":"2018","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.nucmedbio.2012.04.007","article-title":"68Ga-BPAMD: PET-imaging of bone metastases with a generator based positron emitter","volume":"39","author":"Fellner","year":"2012","journal-title":"Nucl. Med. Biol."},{"key":"ref_57","first-page":"98","article-title":"Preparation and Biological Study of 68 Ga-DOTA-alendronate","volume":"4","author":"Fakhari","year":"2016","journal-title":"Asia Ocean J. Nucl. Med. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ashhar, Z., Yusof, N.A., Ahmad Saad, F.F., Mohd Nor, S.M., Mohammad, F., Bahrin Wan Kamal, W.H., Hassan, M.H., Ahmad Hassali, H., and Al-Lohedan, H.A. (2020). Preparation, Characterization, and Radiolabeling of [(68)Ga]Ga-NODAGA-Pamidronic Acid: A Potential PET Bone Imaging Agent. Molecules, 25.","DOI":"10.3390\/molecules25112668"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Park, P.S.U., Raynor, W.Y., Sun, Y., Werner, T.J., Rajapakse, C.S., and Alavi, A. (2021). 18F-sodium fluoride pet as a diagnostic modality for metabolic, autoimmune, and osteogenic bone disorders: Cellular mechanisms and clinical applications. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126504"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4103\/2231-0746.92790","article-title":"High-grade chondroblastic and fibroblastic osteosarcoma of the upper jaw","volume":"1","author":"Cutilli","year":"2011","journal-title":"Ann. Maxillofac. Surg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"235","DOI":"10.5624\/isd.2019.49.3.235","article-title":"V Radiographic manifestations of fibroblastic osteosarcoma: A diagnostic challenge","volume":"49","author":"Barnts","year":"2019","journal-title":"Imaging Sci. Dent."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"101554","DOI":"10.1016\/j.jksus.2021.101554","article-title":"Multivariate optimisation and validation of the analytical GC-FID for evaluating organic solvents in radiopharmaceutical","volume":"33","author":"Hassan","year":"2021","journal-title":"J. King Saud Univ. -Sci."},{"key":"ref_63","unstructured":"IAEA (2021). Guidance for Preclinical Studies with Radiopharmaceuticals, IAEA."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/22\/7969\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:22Z","timestamp":1760145622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/22\/7969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,17]]},"references-count":63,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["molecules27227969"],"URL":"https:\/\/doi.org\/10.3390\/molecules27227969","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,17]]}}}