An improved fully-automated GMP radiosynthesis of [¹⁸F]fluoro-pivalic acid with solid-phase extraction purification
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
We previously reported the first-in-human evaluation of 3-[18F]-fluoro-2,2-dimethylpropionic acid ([18F]FPIA) for imaging aberrant lipid metabolism and cancer detection. The first-generation semi-automated radiosynthesis of [18F]FPIA required HPLC purification to provide injection solution devoid of precursor (methyl 2,2-dimethyl-3-[(4-methylbenzenesulfonyl)oxy]propanoate), radioactive intermediate (methyl-3-([18F]fluoro)-2,2-dimethylpropanoate), and potential chemical impurities (tosic acid, 3-hydroxy-2,2-dimethylpropanoic acid and unlabelled FPIA). In readiness for global use of [18F]FPIA, we report a significant improvement to the GMP production through development of a fully-automated solid-phase extraction (SPE) purification method.
Results
We developed a fully-automated SPE purified radiosynthesis on FASTLab™ for GMP readiness that was translated to and validated on the Trasis AIO™ platform for routine clinical use. Purification of the radiotracer by SPE on both systems was achieved (> 98% radiochemical purity), increasing the radiochemical yield compared to the HPLC-based purification method. Non-decay-corrected radiochemical yields (RCY, n.d.c) were 30.3 ± 2.3% (n = 8) and 25.8 ± 6.6% (n = 46) on GE FASTlab™ and Trasis AIO™, respectively. Non-radioactive FPIA and other analytes determined by HPLC were below the limit of detection (< 1.0 µg/mL) from GE FASTlab™ and ≤ 1.2 µg/mL from Trasis AIO™.
Conclusions
The synthesis of [18F]FPIA was validated on the Trasis AIO™ platform for GMP production and is currently used to produce clinical doses for phase II clinical trials. Readiness for GMP validation was also demonstrated on GE FASTlab™ and can be adopted on other automated platforms.
We previously reported the first-in-human evaluation of 3-[18F]-fluoro-2,2-dimethylpropionic acid ([18F]FPIA) for imaging aberrant lipid metabolism and cancer detection. The first-generation semi-automated radiosynthesis of [18F]FPIA required HPLC purification to provide injection solution devoid of precursor (methyl 2,2-dimethyl-3-[(4-methylbenzenesulfonyl)oxy]propanoate), radioactive intermediate (methyl-3-([18F]fluoro)-2,2-dimethylpropanoate), and potential chemical impurities (tosic acid, 3-hydroxy-2,2-dimethylpropanoic acid and unlabelled FPIA). In readiness for global use of [18F]FPIA, we report a significant improvement to the GMP production through development of a fully-automated solid-phase extraction (SPE) purification method.
Results
We developed a fully-automated SPE purified radiosynthesis on FASTLab™ for GMP readiness that was translated to and validated on the Trasis AIO™ platform for routine clinical use. Purification of the radiotracer by SPE on both systems was achieved (> 98% radiochemical purity), increasing the radiochemical yield compared to the HPLC-based purification method. Non-decay-corrected radiochemical yields (RCY, n.d.c) were 30.3 ± 2.3% (n = 8) and 25.8 ± 6.6% (n = 46) on GE FASTlab™ and Trasis AIO™, respectively. Non-radioactive FPIA and other analytes determined by HPLC were below the limit of detection (< 1.0 µg/mL) from GE FASTlab™ and ≤ 1.2 µg/mL from Trasis AIO™.
Conclusions
The synthesis of [18F]FPIA was validated on the Trasis AIO™ platform for GMP production and is currently used to produce clinical doses for phase II clinical trials. Readiness for GMP validation was also demonstrated on GE FASTlab™ and can be adopted on other automated platforms.
Date Issued
2026-12-01
Date Acceptance
2026-03-05
Citation
EJNMMI Radiopharmacy and Chemistry, 2026, 11 (1)
ISSN
2365-421X
Publisher
SpringerOpen
Journal / Book Title
EJNMMI Radiopharmacy and Chemistry
Volume
11
Issue
1
Copyright Statement
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1186/s41181-026-00440-4
Subjects
18 F]FPIA
[ 18 F]fluoropivalic acid
GMP radiopharmaceutical
Automated radiosynthesis
SPE purification
PET/positron emission tomography
Fluorine-18
Publication Status
Published
Article Number
31
Date Publish Online
2026-03-21