Simple Synthesis of [18F] AV-45 and its Clinical Application in the Diagnosis of Alzheimer's Disease
- Authors: Zhang Q.1, Yilihamu N.2, Li Y.1, Li X.2, Qin Y.1
-
Affiliations:
- Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University
- Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University
- Issue: Vol 31, No 10 (2024)
- Pages: 1278-1288
- Section: Anti-Infectives and Infectious Diseases
- URL: https://rjmseer.com/0929-8673/article/view/644163
- DOI: https://doi.org/10.2174/0929867331666230731123226
- ID: 644163
Cite item
Full Text
Abstract
Objective:[18F] AV-45 can be produced in a simple, stable, and repeatable manner on the Tracerlab FXF-N platform using a self-editing synthetic procedure and solid-phase extraction purification method. This technique is applied to positron emission tomography (PET) imaging of Alzheimer's disease (AD) to observe its distribution and characteristics in various brain regions and its diagnostic efficiency for the disease.
Methods:The precursor was subjected to nucleophilic radiofluorination at 120 °C in anhydrous dimethyl sulfoxide, followed by acid hydrolysis of the protecting groups. The neutralized reaction mixture was purified by solid phase extraction to obtain a relatively pure [18F] AV-45 product with a high specific activity. A total of 10 participants who were diagnosed with Alzheimer's disease (AD group) and 10 healthy controls (HC group) were included retrospectively. All of them underwent [18F] AV-45 brain PET/CT imaging. The distribution of [18F] AV-45 in the AD group was analyzed visually and semi-quantitatively.
Results:Six consecutive radiochemical syntheses were performed in this experiment. The average production time of [18F] AV-45 was 52 minutes, the radiochemical yield was 14.2 % ± 2.7% (n = 6), and the radiochemical purity was greater than 95%. When used with PET/CT imaging, the results of the visual analysis indicated increased [18F] AV-45 radioactivity uptake in the frontal, temporal, and parietal lobes in AD patients. Semiquantitative analysis showed the highest diagnostic efficacy in the posterior cingulate gyrus compared with other brain regions (p < 0.001).
Conclusion:Intravenous [18F] AV-45 was successfully prepared on the Tracerlab FXF-N platform by solid-phase extraction of crude product and automated radiochemical synthesis. PET/CT imaging can be used to diagnose and evaluate AD patients and provide a more robust basis for clinicians to diagnose AD.
About the authors
Qi-Zhou Zhang
Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University
Email: info@benthamscience.net
Nazi Yilihamu
Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University
Email: info@benthamscience.net
Yu-Bin Li
Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University
Email: info@benthamscience.net
Xiao-Hong Li
Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University
Email: info@benthamscience.net
Yong-De Qin
Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University
Author for correspondence.
Email: info@benthamscience.net
References
- Weidner, W.S.; Barbarino, P. Thestate of the art of dementia research: New frontiers. Alzheimers Dement., 2019, 15(7), P1473. doi: 10.1016/j.jalz.2019.06.4115
- Zhang, Y.L.; Hu, X.L.; Li, Y.H.; Zhao, C.X. International clinical practice guideline of Chinese medicine Alzheimer. World J. Tradit. Chin. Med., 2021, 7, 265-275.
- Levin, O.S.; Vasenina, E.E. 25 Years of the amyloid hypothesis of the origin of Alzheimers disease: Advances, failures, and new perspectives. Neurosci. Behav. Physiol., 2017, 47(9), 1065-1070. doi: 10.1007/s11055-017-0513-0
- Litvinenko, I.V.; Emelin, A.Y.; Lobzin, V.Y. he amyloid hypothesis of Alzheimers disease: Past and present, hopes and disappointments. Neurology neuropsychiatry. Psychosomatics, 2019, 11(3), 4-10.
- Rinne, J.O.; Brooks, D.J.; Rossor, M.N.; Fox, N.C.; Bullock, R.; Klunk, W.E.; Mathis, C.A.; Blennow, K.; Barakos, J.; Okello, A.A.; de LIano, S.R.M.; Liu, E.; Koller, M.; Gregg, K.M.; Schenk, D.; Black, R.; Grundman, M. 11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimers disease treated with bapineuzumab: A phase 2, double-blind, placebo- controlled, ascending-dose study. Lancet Neurol., 2010, 9(4), 363-372. doi: 10.1016/S1474-4422(10)70043-0 PMID: 20189881
- Liu, E.; Schmidt, M.E.; Margolin, R.; Sperling, R.; Koeppe, R.; Mason, N.S.; Klunk, W.E.; Mathis, C.A.; Salloway, S.; Fox, N.C.; Hill, D.L.; Les, A.S.; Collins, P.; Gregg, K.M.; Di, J.; Lu, Y.; Tudor, I.C.; Wyman, B.T.; Booth, K.; Broome, S.; Yuen, E.; Grundman, M.; Brashear, H.R. Amyloid-β11 C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials. Neurology, 2015, 85(8), 692-700. doi: 10.1212/WNL.0000000000001877 PMID: 26208959
- Koole, M.; Lewis, D.M.; Buckley, C.; Nelissen, N.; Vandenbulcke, M.; Brooks, D.J.; Vandenberghe, R.; Van Laere, K. Whole-body biodistribution and radiation dosimetry of 18F-GE067: A radioligand for in vivo brain amyloid imaging. J. Nucl. Med., 2009, 50(5), 818-822. doi: 10.2967/jnumed.108.060756 PMID: 19372469
- Snellman, A.; Rokka, J.; López-Picón, F.R.; Eskola, O.; Salmona, M.; Forloni, G.; Scheinin, M.; Solin, O.; Rinne, J.O.; Haaparanta-Solin, M. In vivo PET imaging of beta-amyloid deposition in mouse models of Alzheimers disease with a high specific activity PET imaging agent 18Fflutemetamol. EJNMMI Res., 2014, 4(1), 37. doi: 10.1186/s13550-014-0037-3 PMID: 25977876
- Sabri, O.; Sabbagh, M.N.; Seibyl, J.; Barthel, H.; Akatsu, H.; Ouchi, Y.; Senda, K.; Murayama, S.; Ishii, K.; Takao, M.; Beach, T.G.; Rowe, C.C.; Leverenz, J.B.; Ghetti, B.; Ironside, J.W.; Catafau, A.M.; Stephens, A.W.; Mueller, A.; Koglin, N.; Hoffmann, A.; Roth, K.; Reininger, C.; Schulz-Schaeffer, W.J. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimers disease: Phase 3 study. Alzheimers Dement., 2015, 11(8), 964-974. doi: 10.1016/j.jalz.2015.02.004 PMID: 25824567
- Devous, M.D., Sr; Fleisher, A.S.; Pontecorvo, M.J.; Lu, M.; Siderowf, A.; Navitsky, M.; Kennedy, I.; Southekal, S.; Harris, T.S.; Mintun, M.A. Relationships between cognition and neuropathological tau in Alzheimers disease assessed by 18F flortaucipir PET. J. Alzheimers Dis., 2021, 80(3), 1091-1104. doi: 10.3233/JAD-200808 PMID: 33682705
- Chandra, A.; Valkimadi, P.E.; Pagano, G.; Cousins, O.; Dervenoulas, G.; Politis, M. Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimers disease and mild cognitive impairment. Hum. Brain Mapp., 2019, 40(18), 5424-5442. doi: 10.1002/hbm.24782 PMID: 31520513
- Nakamura, T.; Iwata, A.; Ueda, K.; Namiki, C. Clinical implications and appropriate use of amyloid imaging with florbetapir (18F) in diagnosis of patients with Alzheimer disease. Brain Nerve, 2016, 68(10), 1215-1222. PMID: 27703109
- Asghar, M.; Hinz, R.; Herholz, K.; Carter, S.F. Dual-phase 18Fflorbetapir in frontotemporal dementia. Eur. J. Nucl. Med. Mol. Imaging, 2019, 46(2), 304-311. doi: 10.1007/s00259-018-4238-2 PMID: 30569187
- Soffers, F.; Ceyssens, S.; Buffet, W.; de Surgeloose, D.; Crols, R. 18F-florbetapir PET in primary cerebral amyloidoma. Clin. Nucl. Med., 2020, 45(10), 838-839. doi: 10.1097/RLU.0000000000003214 PMID: 32796236
- Bateman, R.J.; Xiong, C.; Benzinger, T.L.S.; Fagan, A.M.; Goate, A.; Fox, N.C.; Marcus, D.S.; Cairns, N.J.; Xie, X.; Blazey, T.M.; Holtzman, D.M.; Santacruz, A.; Buckles, V.; Oliver, A.; Moulder, K.; Aisen, P.S.; Ghetti, B.; Klunk, W.E.; McDade, E.; Martins, R.N.; Masters, C.L.; Mayeux, R.; Ringman, J.M.; Rossor, M.N.; Schofield, P.R.; Sperling, R.A.; Salloway, S.; Morris, J.C. Clinical and biomarker changes in dominantly inherited Alzheimers disease. N. Engl. J. Med., 2012, 367(9), 795-804. doi: 10.1056/NEJMoa1202753 PMID: 22784036
- Fleisher, A.S.; Chen, K.; Quiroz, Y.T.; Jakimovich, L.J.; Gutierrez Gomez, M.; Langois, C.M.; Langbaum, J.B.S.; Roontiva, A.; Thiyyagura, P.; Lee, W.; Ayutyanont, N.; Lopez, L.; Moreno, S.; Muñoz, C.; Tirado, V.; Acosta-Baena, N.; Fagan, A.M.; Giraldo, M.; Garcia, G.; Huentelman, M.J.; Tariot, P.N.; Lopera, F.; Reiman, E.M. Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: A cross-sectional study. JAMA Neurol., 2015, 72(3), 316-324. doi: 10.1001/jamaneurol.2014.3314 PMID: 25580592
- Donohue, M.C.; Jacqmin-Gadda, H.; Le Goff, M.; Thomas, R.G.; Raman, R.; Gamst, A.C.; Beckett, L.A.; Jack, C.R., Jr; Weiner, M.W.; Dartigues, J.F.; Aisen, P.S. Estimating long-term multivariate progression from short-term data. Alzheimers Dement., 2014, 10(5S)(Suppl.), S400-S410. doi: 10.1016/j.jalz.2013.10.003 PMID: 24656849
- Young, A.L.; Oxtoby, N.P.; Daga, P.; Cash, D.M.; Fox, N.C.; Ourselin, S.; Schott, J.M.; Alexander, D.C. A data- driven model of biomarker changes in sporadic Alzheimers disease. Brain, 2014, 137(9), 2564-2577. doi: 10.1093/brain/awu176 PMID: 25012224
- Xiong, C.; Jasielec, M.S.; Weng, H.; Fagan, A.M.; Benzinger, T.L.S.; Head, D.; Hassenstab, J.; Grant, E.; Sutphen, C.L.; Buckles, V.; Moulder, K.L.; Morris, J.C. Longitudinal relationships among biomarkers for Alzheimer disease in the adult children study. Neurology, 2016, 86(16), 1499-1506. doi: 10.1212/WNL.0000000000002593 PMID: 27009258
- Jack, C.R., Jr; Bennett, D.A.; Blennow, K.; Carrillo, M.C.; Dunn, B.; Haeberlein, S.B.; Holtzman, D.M.; Jagust, W.; Jessen, F.; Karlawish, J.; Liu, E.; Molinuevo, J.L.; Montine, T.; Phelps, C.; Rankin, K.P.; Rowe, C.C.; Scheltens, P.; Siemers, E.; Snyder, H.M.; Sperling, R.; Elliott, C.; Masliah, E.; Ryan, L.; Silverberg, N. NIA-AA research framework: Toward a biological definition of Alzheimers disease. Alzheimers Dement., 2018, 14(4), 535-562. doi: 10.1016/j.jalz.2018.02.018 PMID: 29653606
- Ismail, Z.; Black, S.E.; Camicioli, R.; Chertkow, H.; Herrmann, N.; Laforce, R., Jr; Montero-Odasso, M.; Rockwood, K.; Rosa-Neto, P.; Seitz, D.; Sivananthan, S.; Smith, E.E.; Soucy, J.P.; Vedel, I.; Gauthier, S. Recommendations of the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia. Alzheimers Dement., 2020, 16(8), 1182-1195. doi: 10.1002/alz.12105 PMID: 32725777
- Lee, J.S.; Kim, G.H.; Kim, H.J.; Kim, H.J.; Na, S.; Park, K.H.; Park, Y.H.; Suh, J. Shin, J.H.; Oh, S.I.; Yoon, B. Clinical practice guideline for dementia (diagnosis and evaluation): 2021 revised edition. Dement Neurocogn. Disord., 2022, 21(1), 42-44.
- Shiino, A.; Shirakashi, Y.; Ishida, M.; Tanigaki, K. Machine learning of brain structural biomarkers for Alzheimers disease (AD) diagnosis, prediction of disease progression, and amyloid beta deposition in the Japanese population. Alzheimers Dement. (Amst.), 2021, 13(1), e12246. doi: 10.1002/dad2.12246 PMID: 34692983
- Spencer, B.E.; Jennings, R.G.; Brewer, J.B. Combined biomarker prognosis of mild cognitive impairment: An 11-year follow-up study in the Alzheimers disease neuroimaging initiative. J. Alzheimers Dis., 2019, 68(4), 1549-1559. doi: 10.3233/JAD-181243 PMID: 30958366
- Writing Goup of the Dementia and Cognitive Society of Neurology Committee of Chinese Medical Association. Guidelines for dementia and cognitive impairment in China: The diagnosis and treatment of mild cognitive impairment Zhonghua Yi Xue Za Zhi, 2018, 98(13), 7.
- Morris, E.; Chalkidou, A.; Hammers, A.; Peacock, J.; Summers, J.; Keevil, S. Diagnostic accuracy of 18F amyloid PET tracers for the diagnosis of Alzheimers disease: A systematic review and meta-analysis. Eur. J. Nucl. Med. Mol. Imaging, 2016, 43(2), 374-385. doi: 10.1007/s00259-015-3228-x PMID: 26613792
- Zhang, C.; Wang, C.; Xin, M. Value of visual analysis and SUVR during ^18F-AV45 PET/CT imaging in the diagnosis of mild cognitive impairment and Alzheimer′s disease. Chin. J. Nucl. Med. Mol. Imaging, 2020, 40(4), 201-206.
- Zhang, L.; Zhang, A.; Yao, X.; Zhang, Y.; Liu, F.; Hong, H.; Zha, Z.; Liu, Y.; Wu, Z.; Qiao, J.; Zhu, L.; Kung, H.F. An improved preparation of 18FAV-45 by simplified solid-phase extraction purification. J. Labelled Comp. Radiopharm., 2020, 63(3), 108-118. doi: 10.1002/jlcr.3813 PMID: 31697847
- Zhang, Q.Z.; Li, Y.B.; Yilihamu, N.; Li, X.H.; Ba, Y.; Qin, Y.D. Optimization of automatic synthesis and separation of 18F AV-45 and quality control. Front Chem., 2022, 10, 826678. doi: 10.3389/fchem.2022.826678 PMID: 35494660
- Han, P.; Shi, J. A theoretical analysis of the synergy of amyloid and tau in Alzheimers disease. J. Alzheimers Dis., 2016, 52(4), 1461-1470. doi: 10.3233/JAD-151206 PMID: 27104897
- Zhu, Z.; Zhu, H. Research progress in imaging agents targeting Aβ and Tau protein in Alzheimers disease Z. Chin J Nucl Med Mol Imaging, 2018, 38(4), 291-294.
- Trembath, L.; Newell, M.; Devous, M.D., Sr Technical considerations in brain amyloid PET imaging with 18 F-florbetapir. J. Nucl. Med. Technol., 2015, 43(3), 175-184. doi: 10.2967/jnmt.115.156679 PMID: 26271806
- Veitch, D.P.; Weiner, M.W.; Aisen, P.S.; Beckett, L.A.; DeCarli, C.; Green, R.C.; Harvey, D.; Jack, C.R., Jr; Jagust, W.; Landau, S.M.; Morris, J.C.; Okonkwo, O.; Perrin, R.J.; Petersen, R.C.; Rivera-Mindt, M.; Saykin, A.J.; Shaw, L.M.; Toga, A.W.; Tosun, D.; Trojanowski, J.Q. Using the Alzheimers disease neuroimaging initiative to improve early detection, diagnosis, and treatment of Alzheimers disease. Alzheimers Dement., 2022, 18(4), 824-857. doi: 10.1002/alz.12422 PMID: 34581485
- Mukherjee, S.; Mez, J.; Trittschuh, E.H.; Saykin, A.J.; Gibbons, L.E.; Fardo, D.W.; Wessels, M.; Bauman, J.; Moore, M.; Choi, S.E.; Gross, A.L.; Rich, J.; Louden, D.K.N.; Sanders, R.E.; Grabowski, T.J.; Bird, T.D.; McCurry, S.M.; Snitz, B.E.; Kamboh, M.I.; Lopez, O.L.; De Jager, P.L.; Bennett, D.A.; Keene, C.D.; Larson, E.B.; Crane, P.K. Genetic data and cognitively defined late-onset Alzheimers disease subgroups. Mol. Psychiatry, 2020, 25(11), 2942-2951. doi: 10.1038/s41380-018-0298-8 PMID: 30514930
Supplementary files
