Neuroinflammation in Low-Level PM2.5-Exposed Rats Illustrated by PET via an Improved Automated Produced [18F]FEPPA: A Feasibility Study

Background. [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of t...

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Published inMolecular imaging Vol. 2022
Main Authors Cheng, Mei-Fang, Cheng, Tsun-Jen, Guo, Yue Leon, Chiu, Ching-Hung, Wu, Hung-Ming, Yen, Ruoh-Fang, Huang, Ya-Yao, Huang, Wen-Sheng, Shiue, Chyng-Yann
Format Journal Article
LanguageEnglish
Published Thousand Oaks Hindawi 2022
Sage Publications Ltd
SAGE Publishing
Subjects
Automation
Brain
Cyclotrons
Exposure
Feasibility studies
Fluorine isotopes
High-performance liquid chromatography
Imaging
Inflammation
Liquid chromatography
Neuroimaging
Particulate matter
Positron emission
Positron emission tomography
Purification
Radiochemistry
Stability criteria
Stability tests
Synthesis
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Abstract Background. [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats. Results. Using this automated synthesis method, the RCY of the [18F]FEPPA was 38±4% (n=17, EOB) in a synthesis time of 83±8 min from EOB. The radiochemical purity and molar activities were greater than 99% and 209±138 GBq/μmol (EOS, n=15), respectively. The quality of the [18F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]FEPPA was stable at 21±2°C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [18F]FEPPA in the brain of PM2.5-exposed rats (n=6) were higher than that of normal controls (n=6) and regional-specific. Conclusions. Using the improved semipreparative HPLC purification, [18F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.
AbstractList Background. [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats. Results. Using this automated synthesis method, the RCY of the [18F]FEPPA was 38±4% (n=17, EOB) in a synthesis time of 83±8 min from EOB. The radiochemical purity and molar activities were greater than 99% and 209±138 GBq/μmol (EOS, n=15), respectively. The quality of the [18F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]FEPPA was stable at 21±2°C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [18F]FEPPA in the brain of PM2.5-exposed rats (n=6) were higher than that of normal controls (n=6) and regional-specific. Conclusions. Using the improved semipreparative HPLC purification, [18F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.
Background. [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats. Results. Using this automated synthesis method, the RCY of the [18F]FEPPA was 38 ± 4 % ( n = 17 , EOB) in a synthesis time of 83 ± 8  min from EOB. The radiochemical purity and molar activities were greater than 99% and 209 ± 138  GBq/μmol (EOS, n = 15 ), respectively. The quality of the [18F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]FEPPA was stable at 21 ± 2 °C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [18F]FEPPA in the brain of PM2.5-exposed rats ( n = 6 ) were higher than that of normal controls ( n = 6 ) and regional-specific. Conclusions. Using the improved semipreparative HPLC purification, [18F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.
Background. [ 18 F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats. Results. Using this automated synthesis method, the RCY of the [ 18 F]FEPPA was [Formula: see text] ([Formula: see text], EOB) in a synthesis time of [Formula: see text] min from EOB. The radiochemical purity and molar activities were greater than 99% and [Formula: see text] GBq/ μmol (EOS, [Formula: see text]), respectively. The quality of the [ 18 F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [ 18 F]FEPPA was stable at [Formula: see text]°C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [ 18 F]FEPPA in the brain of PM2.5-exposed rats ([Formula: see text]) were higher than that of normal controls ([Formula: see text]) and regional-specific. Conclusions. Using the improved semipreparative HPLC purification, [ 18 F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.
Background. [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats. Results. Using this automated synthesis method, the RCY of the [18F]FEPPA was 38 ± 4 % ( n = 17 , EOB) in a synthesis time of 83 ± 8  min from EOB. The radiochemical purity and molar activities were greater than 99% and 209 ± 138  GBq/μmol (EOS, n = 15 ), respectively. The quality of the [18F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]FEPPA was stable at 21 ± 2 °C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [18F]FEPPA in the brain of PM2.5-exposed rats ( n = 6 ) were higher than that of normal controls ( n = 6 ) and regional-specific. Conclusions. Using the improved semipreparative HPLC purification, [18F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons.
Author Cheng, Tsun-Jen
Huang, Ya-Yao
Guo, Yue Leon
Yen, Ruoh-Fang
Wu, Hung-Ming
Huang, Wen-Sheng
Shiue, Chyng-Yann
Cheng, Mei-Fang
Chiu, Ching-Hung
AuthorAffiliation 7 Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan
2 Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan
4 Molecular Imaging Center, National Taiwan University, Taipei, Taiwan
5 Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan
8 Department of Nuclear Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan
6 Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
1 Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
3 Department of Neurology, Changhua Christian Hospital, Taiwan
9 PET Center, Department of Nuclear Medicine, Tri-Service General Hospital, Taiwan
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CitedBy_id crossref_primary_10_1016_j_chemosphere_2023_139663
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Snippet Background. [18F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the...
Background. [ 18 F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the...
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SubjectTerms Automation
Brain
Cyclotrons
Exposure
Feasibility studies
Fluorine isotopes
High-performance liquid chromatography
Imaging
Inflammation
Liquid chromatography
Neuroimaging
Particulate matter
Positron emission
Positron emission tomography
Purification
Radiochemistry
Stability criteria
Stability tests
Synthesis
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Title Neuroinflammation in Low-Level PM2.5-Exposed Rats Illustrated by PET via an Improved Automated Produced [18F]FEPPA: A Feasibility Study
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