One-pot and one-step automated radio-synthesis of [18F]AlF-FAPI-74 using a multi purpose synthesizer: a proof-of-concept experiment

EJNMMI Radiopharmacy and Chemistry

Thomas Lindner¹  Frederik L. Giesel²  Eku Shimosegawa³  Kenta Kurimoto⁴  Hiroki Kato⁴  Tadashi Watabe⁴  Sadahiro Naka⁵  Yuriko Mori⁶  Jens Cardinale⁶  Frank Valla⁶  Mitsuaki Tatsumi⁷  Melissa Moore⁸ 

[1] Department for Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany;Department for Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany;Department of Nuclear Medicine, University Hospital Düsseldorf, Düsseldorf, Germany;Institute for Radiation Sciences, Osaka University, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan;Department of Radiology, Osaka University Hospital, 2-15 Yamadaoka, 565-0871, Suita, Osaka, Japan;Department of Nuclear Medicine, University Hospital Düsseldorf, Düsseldorf, Germany;Department of Radiology, Osaka University Hospital, 2-15 Yamadaoka, 565-0871, Suita, Osaka, Japan;SOFIE, 21000 Atlantic Boulevard Suite 730, 20166, Dulles, VA, USA;

关键词: Positron emission tomography;    Fibroblast activation protein;    [F]AlF-FAPI-74;    Automated synthesis;   

DOI  :  10.1186/s41181-021-00142-z

来源: Springer

【 摘 要 】

BackgroundFibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [18F]AlF-FAPI-74 is a positron emission tomography tracer with high selectivity for FAP, which has already shown high accumulation within human tumors in clinical studies. However, [18F]AlF-FAPI-74 radiosynthesis has not been optimized using an automated synthesizer. Herein, we report a one-pot and one-step automated radiosynthesis method using a multi purpose synthesizer.ResultsRadiosynthesis of [18F]AlF-FAPI-74 was performed using a cassette-type multi purpose synthesizer CFN-MPS200. After the recovery rate of trapped [18F]fluoride onto the anion-exchange cartridge using a small amount of eluent was investigated manually, a dedicated [18F]AlF-FAPI-74 synthesis cassette and synthesis program for one-pot and one-step fluorination was developed. The solutions for the formulation of [18F]AlF-FAPI-74 synthesized using this were evaluated to obtain stable radiochemical purity. The recovery rate of [18F]fluoride with only 300 µL of eluent ranged 90 ± 9% by introduction from the male side and elution from the female side of the cartridge. In automated synthesis, the eluted [18F]fluoride and precursor solution containing aluminum chloride were mixed; then, fluorination was performed in a one-pot and one-step process at room temperature for 5 min, followed by 15 min at 95 °C. As a result, the radioactivity of [18F]AlF-FAPI-74 was 11.3 ± 1.1 GBq at the end of synthesis from 32 to 40 GBq of [18F]fluoride, and its radiochemical yield was 37 ± 4% (n = 10). The radiochemical purity at the end of the synthesis was ≥ 97% for all formulation solutions. When the diluent was saline, the radiochemical purity markedly decreased after 4 h of synthesis. In contrast, with phosphate-buffered saline (pH 7.4) or 10 mM phosphate-buffered saline (pH 6.7) containing 100 mg of sodium ascorbate, the radiochemical purity was stable at 97%. Non-radioactive AlF-FAPI-74 and total impurities, including non-radioactive AlF-FAPI-74, were 0.3 ± 0.1 µg/mL and 2.8 ± 0.6 µg/mL. Ethanol concentration and residual DMSO were 5.5 ± 0.2% and 21 ± 6 ppm, respectively.ConclusionsWe established a one-pot one-step automated synthesis method using a CFN-MPS200 synthesizer that provided high radioactivity and stable radiochemical purity for possible clinical applications.

【 授权许可】

CC BY