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Tytuł:
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Preliminary studies of an imidazole-based alcohol derivative for imaging of Heme oxygenase 1.
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Autorzy:
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Xu Y; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States.
Liu Y; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States; School of Pharmacy, Lanzhou University, Donggang West Road No. 199, Lanzhou 730020, PR China.
Striar R; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States.
Langan A; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States.
Kate Rattray A; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States.
Afshar S; Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States.
Wang C; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States. Electronic address: .
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Źródło:
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Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2022 May 15; Vol. 64, pp. 128674. Date of Electronic Publication: 2022 Mar 12.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Elsevier Science Ltd
Original Publication: Oxford ; New York : Pergamon Press, c1991-
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MeSH Terms:
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Heme Oxygenase-1*/metabolism
Positron Emission Tomography Computed Tomography*/methods
Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Imidazoles/metabolism ; Imidazoles/pharmacology ; Mice ; Mice, Inbred C57BL ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/metabolism
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Grant Information:
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P41 EB015896 United States EB NIBIB NIH HHS; S10 OD025234 United States OD NIH HHS; S10 RR017208 United States RR NCRR NIH HHS; S10 RR026666 United States RR NCRR NIH HHS; S10 RR022976 United States RR NCRR NIH HHS; S10 RR019933 United States RR NCRR NIH HHS; S10 RR023401 United States RR NCRR NIH HHS; S10 OD023517 United States OD NIH HHS
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Contributed Indexing:
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Keywords: Alzheimer's disease (AD); Autoradiography; Heme oxygenase-1 (HO-1); PET/CT imaging; [(11)C]QC-33
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Substance Nomenclature:
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0 (Imidazoles)
0 (Radiopharmaceuticals)
EC 1.14.14.18 (Heme Oxygenase-1)
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Entry Date(s):
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Date Created: 20220316 Date Completed: 20220405 Latest Revision: 20220508
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Update Code:
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20240105
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DOI:
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10.1016/j.bmcl.2022.128674
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PMID:
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35292342
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Heme oxygenase-1 (HO-1) has been involved in the pathogenesis of Alzheimer's disease (AD), thus constituting a promising target for AD drug development. Positron emission tomography (PET) is a fully translational imaging technology, which will help us understand the role of HO-1 in the progression of AD, facilitating to validate promising HO-1 inhibitors in clinical trials. To our knowledge, there is no report on PET imaging probe targeting HO-1 in animals and humans. We report herein the synthesis and characterization of a 11 C-labeled imidazole-based alcohol derivative ([ 11 C]QC-33) for imaging of HO-1 in the brain. The desired product [ 11 C]QC-33 was afforded with a radiochemical yield of 16 ± 9% (n = 3, decay corrected). The radiochemical purity was greater than 99%, and the molar radioactivity was greater than 185 GBq/μmol. In vitro autoradiography studies indicated specific binding of [ 11 C]QC-33 in the HO-1 rich regions, showing 75%, 75%, and 69% radioactivity binding reductions in cerebellum, brain stem, and midbrain, respectively. PET/CT scanning in C57BL/6 mice showed low brain uptake and poor blood-brain barrier (BBB) penetration of [ 11 C]QC-33. These results suggested that [ 11 C]QC-33 can serve as a lead compound to advance the development of next generation PET tracer with the potential to monitor HO-1 in AD progression.
(Copyright © 2022. Published by Elsevier Ltd.)
