Copper-Mediated Radiofluorination of the Excitatory Amino Acid Transporter 2 (EAAT2)-Targeted PET Tracer [¹⁸F]RP-115: Alternate Synthetic Method.
- 1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
- 2Rio Pharmaceuticals, Inc., San Francisco, California, USA.
Abstract
Excitatory amino acid transporter 2 (EAAT2) is a key regulator of extracellular glutamate in the central nervous system. Dysregulated EAAT2 is implicated in neurodegenerative diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), highlighting EAAT2 as a potential target for PET imaging. We previously reported a multistep radiosynthesis of [¹⁸F]RP-115, a CNS-permeable prodrug that undergoes esterase-mediated hydrolysis in the CNS to yield the active EAAT2-binding carboxylate. Motivated by recent advances in copper-mediated radiofluorination (CMRF), we sought to develop a more efficient late-stage radiosynthesis of [¹⁸F]RP-115. A two-step radiosynthesis of [¹⁸F]RP-115 using CMRF provided [¹⁸F]RP-115 in high radiochemical yield (52.8% ± 2.1 %, decay-corrected from starting [¹⁸F]fluoride ion, n = 4), high molar activity (355 ± 61 GBq/μmol), and high radiochemical purity (> 99%) with a total synthesis time of 70 min. Chiral HPLC analysis demonstrated that the configuration of the aspartic acid residue remained intact without racemization during both the CMRF and trifluoroacetic acid mediated deprotection. We developed an efficient radiosynthesis of [¹⁸F]RP-115 via CMRF, achieving high radiochemical yield and molar activity. This efficient synthesis may serve as a basis for the future implementation of a CMRF-based automated radiosynthesis of [¹⁸F]RP-115.
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BibTeX
@article{lee2026coppermediated,
title = {{Copper-Mediated Radiofluorination of the Excitatory Amino Acid Transporter 2 (EAAT2)-Targeted PET Tracer [¹⁸F]RP-115: Alternate Synthetic Method.}},
author = {Sang Hee Lee and Joseph Blecha and Jung Min Kim and Ryan Michael Nillo and Robert R Flavell and Chih-Kai Chao and John R Forsayeth and John M Gerdes and Henry F VanBrocklin and David M Wilson},
journal = {Journal of labelled compounds \& radiopharmaceuticals},
year = {2026},
month = oct,
doi = {10.1002/jlcr.70044},
url = {https://europepmc.org/article/MED/42952031},
note = {CC BY},
}
RIS
TY - JOUR
TI - Copper-Mediated Radiofluorination of the Excitatory Amino Acid Transporter 2 (EAAT2)-Targeted PET Tracer [¹⁸F]RP-115: Alternate Synthetic Method.
AU - Sang Hee Lee
AU - Joseph Blecha
AU - Jung Min Kim
AU - Ryan Michael Nillo
AU - Robert R Flavell
AU - Chih-Kai Chao
AU - John R Forsayeth
AU - John M Gerdes
AU - Henry F VanBrocklin
AU - David M Wilson
PY - 2026
DA - 2026/10/28
JO - Journal of labelled compounds & radiopharmaceuticals
DO - 10.1002/jlcr.70044
UR - https://europepmc.org/article/MED/42952031
AB - Excitatory amino acid transporter 2 (EAAT2) is a key regulator of extracellular glutamate in the central nervous system. Dysregulated EAAT2 is implicated in neurodegenerative diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), highlighting EAAT2 as a potential target for PET imaging. We previously reported a multistep radiosynthesis of [¹⁸F]RP-115, a CNS-permeable prodrug that undergoes esterase-mediated hydrolysis in the CNS to yield the active EAAT2-binding carboxylate. Motivated by recent advances in copper-mediated radiofluorination (CMRF), we sought to develop a more efficient late-stage radiosynthesis of [¹⁸F]RP-115. A two-step radiosynthesis of [¹⁸F]RP-115 using CMRF provided [¹⁸F]RP-115 in high radiochemical yield (52.8% ± 2.1 %, decay-corrected from starting [¹⁸F]fluoride ion, n = 4), high molar activity (355 ± 61 GBq/μmol), and high radiochemical purity (> 99%) with a total synthesis time of 70 min. Chiral HPLC analysis demonstrated that the configuration of the aspartic acid residue remained intact without racemization during both the CMRF and trifluoroacetic acid mediated deprotection. We developed an efficient radiosynthesis of [¹⁸F]RP-115 via CMRF, achieving high radiochemical yield and molar activity. This efficient synthesis may serve as a basis for the future implementation of a CMRF-based automated radiosynthesis of [¹⁸F]RP-115.
SN - 0362-4803
SN - 1099-1344
ER -