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Evaluation of [18F]fluoroestradiol and ChRERα as a gene expression PET reporter system in rhesus monkey brain.
Li, Bing; Wadhwa, Palak; Lerchner, Walter; Zanotti-Fregonara, Paolo; Liow, Jeih-San; Yan, Xuefeng; Zoghbi, Sami S; Nerella, Sridhar Goud; Telu, Sanjay; Morse, Cheryl L; Solis, Oscar; Gomez, Juan L; Holt, Daniel P; Dannals, Robert F; Cummins, Alex C; Innis, Robert B; Pike, Victor W; Richmond, Barry J; Michaelides, Michael; Eldridge, Mark A G.
Affiliation
  • Li B; Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Wadhwa P; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Lerchner W; Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Zanotti-Fregonara P; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Liow JS; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Yan X; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Zoghbi SS; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Nerella SG; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Telu S; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Morse CL; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Solis O; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
  • Gomez JL; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
  • Holt DP; Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • Dannals RF; Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • Cummins AC; Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Innis RB; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Pike VW; Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Richmond BJ; Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA.
  • Michaelides M; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: mike.michaelides@nih.gov.
  • Eldridge MAG; Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20814, USA. Electronic address: mark.eldridge@nih.gov.
Mol Ther ; 32(7): 2223-2231, 2024 Jul 03.
Article in En | MEDLINE | ID: mdl-38796702
ABSTRACT
Positron emission tomography (PET) reporter systems are a valuable means of estimating the level of expression of a transgene in vivo. For example, the safety and efficacy of gene therapy approaches for the treatment of neurological and neuropsychiatric disorders could be enhanced via the monitoring of exogenous gene expression levels in the brain. The present study evaluated the ability of a newly developed PET reporter system [18F]fluoroestradiol ([18F]FES) and the estrogen receptor-based PET reporter ChRERα, to monitor expression levels of a small hairpin RNA (shRNA) designed to suppress choline acetyltransferase (ChAT) expression in rhesus monkey brain. The ChRERα gene and shRNA were expressed from the same transcript via lentivirus injected into monkey striatum. In two monkeys that received injections of viral vector, [18F]FES binding increased by 70% and 86% at the target sites compared with pre-injection, demonstrating that ChRERα expression could be visualized in vivo with PET imaging. Post-mortem immunohistochemistry confirmed that ChAT expression was significantly suppressed in regions in which [18F]FES uptake was increased. The consistency between PET imaging and immunohistochemical results suggests that [18F]FES and ChRERα can serve as a PET reporter system in rhesus monkey brain for in vivo evaluation of the expression of potential therapeutic agents, such as shRNAs.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Genes, Reporter / Positron-Emission Tomography / Estradiol / Macaca mulatta Limits: Animals / Humans Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2024 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Genes, Reporter / Positron-Emission Tomography / Estradiol / Macaca mulatta Limits: Animals / Humans Language: En Journal: Mol Ther Journal subject: BIOLOGIA MOLECULAR / TERAPEUTICA Year: 2024 Document type: Article Affiliation country: United States