Nuclear medicine and biology · 2026
Implemented one-pot two step fully automated synthesis of [18F]FPIA for metabolic imaging applications.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Enriquez José S, Paolillo Vincenzo, Armijo Ryan, Morales Aldo, Shepherd Peter D A, Wang Muxin, Bhattacharya Pratip K, Pisaneschi Federica
Аннотация
BACKGROUND: [18F]Fluoropivalate ([18F]FPIA), also known as 18F-pivalate or 18F-RAD101, is the fluorinated analogue of pivalic acid and has shown promise in ongoing clinical trials for the detection of brain metastases. The original synthesis of [18F]FPIA involved a two-step procedure that was not fully automated, limiting its suitability for large-scale or GMP production. A subsequent report described an improved two-step, one-pot synthesis on a cassette-based module, although with certain limitations. Here, we present an optimized two-step, one-pot synthesis of [18F]FPIA using a vial-based automated synthesizer and demonstrate its successful implementation under GMP conditions. We also report [18F]FPIA-PET imaging in prostate cancer patient-derived xenograft (PDX) models.
RESULTS: [18F]FPIA was successfully produced with the optimized synthetic strategy with a total synthesis time of 75 min and a 25.4 ± 3.8% (n = 9) activity yield at end of synthesis (EOS), with >99% radiochemical purity. In a GMP setting, the scale-up synthesis was successful with a 37 ± 9% (n = 37) activity yield at EOS and a > 99% radiochemical purity. In the proof-of-concept PET imaging study of [18F]FPIA in androgen receptor (AR)-negative and -positive prostate cancer PDX animal models, uptake was observed in both groups when the tumor reached a size of 50-300 mm3. The AR-negative group showed significantly higher [18F]FPIA uptake compared to the AR-positive group, with average tumor-to-muscle ratios of 1.6 and 1.2, respectively.
CONCLUSIONS: In summary, an optimized one-pot, two-step synthesis of [18F]FPIA on a vial-based automated synthesizer was successful and a seamless transition into a GMP facility is reported, enabling a streamlined transition to clinical production. Furthermore, we have demonstrated the use of [18F]FPIA for noninvasive metabolic imaging in prostate cancer and its potential to distinguish between different prostate cancer subtypes.
RESULTS: [18F]FPIA was successfully produced with the optimized synthetic strategy with a total synthesis time of 75 min and a 25.4 ± 3.8% (n = 9) activity yield at end of synthesis (EOS), with >99% radiochemical purity. In a GMP setting, the scale-up synthesis was successful with a 37 ± 9% (n = 37) activity yield at EOS and a > 99% radiochemical purity. In the proof-of-concept PET imaging study of [18F]FPIA in androgen receptor (AR)-negative and -positive prostate cancer PDX animal models, uptake was observed in both groups when the tumor reached a size of 50-300 mm3. The AR-negative group showed significantly higher [18F]FPIA uptake compared to the AR-positive group, with average tumor-to-muscle ratios of 1.6 and 1.2, respectively.
CONCLUSIONS: In summary, an optimized one-pot, two-step synthesis of [18F]FPIA on a vial-based automated synthesizer was successful and a seamless transition into a GMP facility is reported, enabling a streamlined transition to clinical production. Furthermore, we have demonstrated the use of [18F]FPIA for noninvasive metabolic imaging in prostate cancer and its potential to distinguish between different prostate cancer subtypes.