Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown rem...Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.展开更多
Background:Fluorine-18 labeled N-(4-chloro-3-(((fluoro-18F)methyl-d2)thio)phenyl)picolinamide,[18F]mG4P027,is a potent positron emission tomogra-phy(PET)radiotracer for mGluR4.Our previous in vitro and in vivo evalua-...Background:Fluorine-18 labeled N-(4-chloro-3-(((fluoro-18F)methyl-d2)thio)phenyl)picolinamide,[18F]mG4P027,is a potent positron emission tomogra-phy(PET)radiotracer for mGluR4.Our previous in vitro and in vivo evalua-tions have demonstrated that this tracer is promising for further translational studies.However,automated radiosynthesis process poses significant chal-lenges that need to be addressed.Methods:The automated radiosynthesis was performed using the TRACER-lab FX2N module,which comprises two distinct reactors capable of accom-modating the two-step reactions.Several problem-solving strategies were employed to overcome challenges during the automation process.This included modifications to the reaction solvents,reaction conditions,use of a scavenger,drying methods,and the handling of the precursor.Results:The use of n-Bu4NN3 for scavenging excess compound 1 along with an efficient drying procedure played a key role in the success of the radio-synthesis.The water was successfully removed by using a different duct to overcome the water sensitivity for the second reaction.Conclusions:Significant modifications were made to the manual process by carefully examining this process and addressing the root causes of the chal-lenges associated with its automation.We successfully implemented auto-mated radiosynthesis using the TRACERlab FX2N module and consequently,obtained a high-purity radiolabeled[18F]mG4P027 in high yield,meeting the requirements for future human studies.展开更多
基金supported by the grants provided by Zhuhai People's Hospital,China(Grant No.:2021KYQD-03)the National Natural Science Foundation of China(Grant No.:22176016).
文摘Fibroblast activation protein(FAP)is overexpressed in cancer-associated fibroblasts across various cancer types.Numerous radiolabeled FAP inhibitors(FAPIs)(Fig.S1A)currently under clinical investigation have shown remarkable potential in cancer theranostics.
文摘Background:Fluorine-18 labeled N-(4-chloro-3-(((fluoro-18F)methyl-d2)thio)phenyl)picolinamide,[18F]mG4P027,is a potent positron emission tomogra-phy(PET)radiotracer for mGluR4.Our previous in vitro and in vivo evalua-tions have demonstrated that this tracer is promising for further translational studies.However,automated radiosynthesis process poses significant chal-lenges that need to be addressed.Methods:The automated radiosynthesis was performed using the TRACER-lab FX2N module,which comprises two distinct reactors capable of accom-modating the two-step reactions.Several problem-solving strategies were employed to overcome challenges during the automation process.This included modifications to the reaction solvents,reaction conditions,use of a scavenger,drying methods,and the handling of the precursor.Results:The use of n-Bu4NN3 for scavenging excess compound 1 along with an efficient drying procedure played a key role in the success of the radio-synthesis.The water was successfully removed by using a different duct to overcome the water sensitivity for the second reaction.Conclusions:Significant modifications were made to the manual process by carefully examining this process and addressing the root causes of the chal-lenges associated with its automation.We successfully implemented auto-mated radiosynthesis using the TRACERlab FX2N module and consequently,obtained a high-purity radiolabeled[18F]mG4P027 in high yield,meeting the requirements for future human studies.
