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Title: Production of diverse PET probes with limited resources: 24 18 F-labeled compounds prepared with a single radiosynthesizer

Abstract

New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Here, despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable “cassettes,” that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis developmentmore » efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting.« less

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ORCiD logo
Publication Date:
Research Org.:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1398833
Alternate Identifier(s):
OSTI ID: 1540265
Grant/Contract Number:  
SC0001249; SC0012353
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 114 Journal Issue: 43; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; Science & Technology; Other Topics; radiosynthesis module; positron-emission tomography; resource efficiency; radiochemistry; PET tracer

Citation Formats

Collins, Jeffrey, Waldmann, Christopher M., Drake, Christopher, Slavik, Roger, Ha, Noel S., Sergeev, Maxim, Lazari, Mark, Shen, Bin, Chin, Frederick T., Moore, Melissa, Sadeghi, Saman, Phelps, Michael E., Murphy, Jennifer M., and van Dam, R. Michael. Production of diverse PET probes with limited resources: 24 18 F-labeled compounds prepared with a single radiosynthesizer. United States: N. p., 2017. Web. doi:10.1073/pnas.1710466114.
Collins, Jeffrey, Waldmann, Christopher M., Drake, Christopher, Slavik, Roger, Ha, Noel S., Sergeev, Maxim, Lazari, Mark, Shen, Bin, Chin, Frederick T., Moore, Melissa, Sadeghi, Saman, Phelps, Michael E., Murphy, Jennifer M., & van Dam, R. Michael. Production of diverse PET probes with limited resources: 24 18 F-labeled compounds prepared with a single radiosynthesizer. United States. doi:10.1073/pnas.1710466114.
Collins, Jeffrey, Waldmann, Christopher M., Drake, Christopher, Slavik, Roger, Ha, Noel S., Sergeev, Maxim, Lazari, Mark, Shen, Bin, Chin, Frederick T., Moore, Melissa, Sadeghi, Saman, Phelps, Michael E., Murphy, Jennifer M., and van Dam, R. Michael. Tue . "Production of diverse PET probes with limited resources: 24 18 F-labeled compounds prepared with a single radiosynthesizer". United States. doi:10.1073/pnas.1710466114.
@article{osti_1398833,
title = {Production of diverse PET probes with limited resources: 24 18 F-labeled compounds prepared with a single radiosynthesizer},
author = {Collins, Jeffrey and Waldmann, Christopher M. and Drake, Christopher and Slavik, Roger and Ha, Noel S. and Sergeev, Maxim and Lazari, Mark and Shen, Bin and Chin, Frederick T. and Moore, Melissa and Sadeghi, Saman and Phelps, Michael E. and Murphy, Jennifer M. and van Dam, R. Michael},
abstractNote = {New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Here, despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable “cassettes,” that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis development efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting.},
doi = {10.1073/pnas.1710466114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 43,
volume = 114,
place = {United States},
year = {2017},
month = {10}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1073/pnas.1710466114

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Cited by: 8 works
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