Compact and cGMP-compliant automated synthesis of [18F]FSPG on the Trasis AllinOne™.

TY - JOUR

T1 - Compact and cGMP-compliant automated synthesis of [18F]FSPG on the Trasis AllinOne™.

AU - Farooq, Rizwan

AU - Gendron, Thibault

AU - Edwards, Richard S

AU - Witney, Timothy H

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/1/17

Y1 - 2025/1/17

N2 - BACKGROUND: (S)-4-(3- 18F-Fluoropropyl)-ʟ-glutamic acid ([ 18F]FSPG) is a positron emission tomography radiotracer used to image system x c -, an antiporter that is upregulated in several cancers. Not only does imaging system x c - with [ 18F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [ 18F]FSPG has been hampered by a lack of robust, cGMP-compliant methods. Here, we report the automated synthesis of [ 18F]FSPG on the Trasis AllinOne™, overcoming previous limitations to provide a user-friendly method ready for clinical adoption. RESULTS: The optimised method provided [ 18F]FSPG in 33.5 ± 4.9% radiochemical yield in just 35 min when starting with 18-25 GBq. Importantly, this method could be scaled up to > 100 GBq starting activity with only a modest reduction in radiochemical yield, providing [ 18F]FSPG with a molar activity of 372 ± 65 GBq/µmol and excellent radiochemical purity (96.8 ± 1.1%). The formulated product was stable when produced with these high starting activities. CONCLUSIONS: We have developed the first automated synthesis of [ 18F]FSPG on the Trasis AllinOne™. The method produces [ 18F]FSPG with excellent radiochemical purity and in high amounts suitable for large clinical trials and off-site distribution. The method expands the number of synthesis modules capable of producing [ 18F]FSPG and has been carefully designed for cGMP compliance to simplify regulatory approval for clinical production. The methods developed for the purification of high-activity [ 18F]FSPG are transferrable and should aid the development of clinical [ 18F]FSPG productions on other synthesis modules.

AB - BACKGROUND: (S)-4-(3- 18F-Fluoropropyl)-ʟ-glutamic acid ([ 18F]FSPG) is a positron emission tomography radiotracer used to image system x c -, an antiporter that is upregulated in several cancers. Not only does imaging system x c - with [ 18F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [ 18F]FSPG has been hampered by a lack of robust, cGMP-compliant methods. Here, we report the automated synthesis of [ 18F]FSPG on the Trasis AllinOne™, overcoming previous limitations to provide a user-friendly method ready for clinical adoption. RESULTS: The optimised method provided [ 18F]FSPG in 33.5 ± 4.9% radiochemical yield in just 35 min when starting with 18-25 GBq. Importantly, this method could be scaled up to > 100 GBq starting activity with only a modest reduction in radiochemical yield, providing [ 18F]FSPG with a molar activity of 372 ± 65 GBq/µmol and excellent radiochemical purity (96.8 ± 1.1%). The formulated product was stable when produced with these high starting activities. CONCLUSIONS: We have developed the first automated synthesis of [ 18F]FSPG on the Trasis AllinOne™. The method produces [ 18F]FSPG with excellent radiochemical purity and in high amounts suitable for large clinical trials and off-site distribution. The method expands the number of synthesis modules capable of producing [ 18F]FSPG and has been carefully designed for cGMP compliance to simplify regulatory approval for clinical production. The methods developed for the purification of high-activity [ 18F]FSPG are transferrable and should aid the development of clinical [ 18F]FSPG productions on other synthesis modules.

UR - http://www.scopus.com/inward/record.url?scp=86000030080&partnerID=8YFLogxK

U2 - 10.1186/s41181-024-00322-7

DO - 10.1186/s41181-024-00322-7

M3 - Article

C2 - 39821860

SN - 2365-421X

VL - 10

SP - 2

JO - EJNMMI Radiopharmacy and Chemistry

JF - EJNMMI Radiopharmacy and Chemistry

IS - 1

M1 - 2

ER -