Radiosynthesis and quality control testing of two ¹⁸F-labeled radiopharmaceuticals for α-synuclein imaging in clinical investigations.
6 affiliations
- 1Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
- 2SHI Accelerator Service Ltd., 7-1-1 Nishigotanda, Shinagawa-ku, Tokyo, 141-0032, Japan.
- 3Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. [email protected].
- 4Tokyo Nuclear Services Co., Ltd., 1-3-5 Taito, Taito-ku, Tokyo, 110-0016, Japan.
- 5Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
- 6Neuroetiology and Diagnostic Science, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno-ku, Osaka, 545-8585, Japan.
Abstract
Background
¹⁸F-Labeled (E)-1-fluoro-3-((2-(4-(5-(methylamino)pyrazin-2-yl)but-1-en-3-yn-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([¹⁸F]SPAL-T-06) and (E)-1-fluoro-3-((2-(4-(6-(methylamino)pyridine-3-yl)but-1-en-3-yn-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([¹⁸F]C05-05) are positron emission tomography (PET) imaging agents for α-synuclein pathologies. Recently, we demonstrated the utility of PET imaging with [¹⁸F]SPAL-T-06 for α-synuclein pathologies in patients with multiple system atrophy and with [¹⁸F]C05-05 for α-synuclein pathologies in Parkinson's disease and related disorders. In this study, to establish [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 as PET radiopharmaceuticals for clinical investigations, we developed routine radiosynthetic procedures using an ¹⁸F-labeling synthesizer and performed quality control (QC) testing of these two PET radiopharmaceuticals.Results
[¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 were synthesized by direct ¹⁸F-fluorination of their respective tetrahydropyranyl-protected tosylated precursors, followed by deprotection, using an ¹⁸F-labeling synthesizer. The non-decay-corrected radiochemical yields of [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 from ¹⁸F⁻ at the end of synthesis (EOS) were 11 ± 4.6% (n = 19) and 20 ± 6.8% (n = 37), respectively. The radiochemical purities of both PET radiopharmaceuticals exceeded 99%. The molar activities of each PET radiopharmaceutical at EOS exceeded 68 GBq/µmol, and the total synthesis times were within 100 min after irradiation. In addition, [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 were efficiently separated from byproducts using a semi-preparative high-performance liquid chromatography system. All QC results for the two PET radiopharmaceuticals complied with in-house QC and quality assurance specifications. The stabilities of the two PET radiopharmaceuticals were evaluated under standard fluorescent light in a general laboratory environment and under UV-cutoff light in a natural light-shielded environment. After 10 min of exposure to the standard fluorescent light, the radiochemical purity of each tracer decreased to approximately 86%. In contrast, the radiochemical purity of each tracer exceeded 99% after 60 min under UV-cutoff light in a natural light-shielded environment.Conclusions
We successfully prepared two PET radiopharmaceuticals, [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05, for clinical investigation. The radiosynthesis and QC findings provide a practical basis for establishing standardized production procedures and facilitating technology transfer to other PET centers. In particularly, all post-deprotection radiosynthesis steps and QC testing for [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 should be performed under UV-cutoff light in a natural light-shielded environment to prevent photoisomerization.
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BibTeX
@article{hashimoto2026radiosynthesis,
title = {{Radiosynthesis and quality control testing of two ¹⁸F-labeled radiopharmaceuticals for α-synuclein imaging in clinical investigations.}},
author = {Hiroki Hashimoto and Takayuki Ohkubo and Kazunori Kawamura and Tomoya Fujishiro and Daisuke Arashi and Tatsuto Sato and Takeru Seki and Masatoshi Muto and Kaito Tsukagoe and Masanao Ogawa and Yusuke Kurihara and Nobuki Nengaki and Wakana Mori and Masayuki Fujinaga and Makoto Higuchi and Ming-Rong Zhang},
journal = {EJNMMI radiopharmacy and chemistry},
year = {2026},
month = jul,
doi = {10.1186/s41181-026-00480-w},
url = {https://europepmc.org/article/MED/42894080},
note = {CC BY},
}
RIS
TY - JOUR
TI - Radiosynthesis and quality control testing of two ¹⁸F-labeled radiopharmaceuticals for α-synuclein imaging in clinical investigations.
AU - Hiroki Hashimoto
AU - Takayuki Ohkubo
AU - Kazunori Kawamura
AU - Tomoya Fujishiro
AU - Daisuke Arashi
AU - Tatsuto Sato
AU - Takeru Seki
AU - Masatoshi Muto
AU - Kaito Tsukagoe
AU - Masanao Ogawa
AU - Yusuke Kurihara
AU - Nobuki Nengaki
AU - Wakana Mori
AU - Masayuki Fujinaga
AU - Makoto Higuchi
AU - Ming-Rong Zhang
PY - 2026
DA - 2026/07/01
JO - EJNMMI radiopharmacy and chemistry
DO - 10.1186/s41181-026-00480-w
UR - https://europepmc.org/article/MED/42894080
AB - Background ¹⁸F-Labeled (E)-1-fluoro-3-((2-(4-(5-(methylamino)pyrazin-2-yl)but-1-en-3-yn-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([¹⁸F]SPAL-T-06) and (E)-1-fluoro-3-((2-(4-(6-(methylamino)pyridine-3-yl)but-1-en-3-yn-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([¹⁸F]C05-05) are positron emission tomography (PET) imaging agents for α-synuclein pathologies. Recently, we demonstrated the utility of PET imaging with [¹⁸F]SPAL-T-06 for α-synuclein pathologies in patients with multiple system atrophy and with [¹⁸F]C05-05 for α-synuclein pathologies in Parkinson's disease and related disorders. In this study, to establish [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 as PET radiopharmaceuticals for clinical investigations, we developed routine radiosynthetic procedures using an ¹⁸F-labeling synthesizer and performed quality control (QC) testing of these two PET radiopharmaceuticals.Results [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 were synthesized by direct ¹⁸F-fluorination of their respective tetrahydropyranyl-protected tosylated precursors, followed by deprotection, using an ¹⁸F-labeling synthesizer. The non-decay-corrected radiochemical yields of [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 from ¹⁸F⁻ at the end of synthesis (EOS) were 11 ± 4.6% (n = 19) and 20 ± 6.8% (n = 37), respectively. The radiochemical purities of both PET radiopharmaceuticals exceeded 99%. The molar activities of each PET radiopharmaceutical at EOS exceeded 68 GBq/µmol, and the total synthesis times were within 100 min after irradiation. In addition, [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 were efficiently separated from byproducts using a semi-preparative high-performance liquid chromatography system. All QC results for the two PET radiopharmaceuticals complied with in-house QC and quality assurance specifications. The stabilities of the two PET radiopharmaceuticals were evaluated under standard fluorescent light in a general laboratory environment and under UV-cutoff light in a natural light-shielded environment. After 10 min of exposure to the standard fluorescent light, the radiochemical purity of each tracer decreased to approximately 86%. In contrast, the radiochemical purity of each tracer exceeded 99% after 60 min under UV-cutoff light in a natural light-shielded environment.Conclusions We successfully prepared two PET radiopharmaceuticals, [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05, for clinical investigation. The radiosynthesis and QC findings provide a practical basis for establishing standardized production procedures and facilitating technology transfer to other PET centers. In particularly, all post-deprotection radiosynthesis steps and QC testing for [¹⁸F]SPAL-T-06 and [¹⁸F]C05-05 should be performed under UV-cutoff light in a natural light-shielded environment to prevent photoisomerization.
SN - 2365-421X
ER -