https://scholars.lib.ntu.edu.tw/handle/123456789/554381
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Shih, Kai-Ting | en_US |
dc.contributor.author | Huang, Ya-Yao | en_US |
dc.contributor.author | Yang, Chia-Ying | en_US |
dc.contributor.author | MEI-FANG CHENG | en_US |
dc.contributor.author | YU-WEN TIEN | en_US |
dc.contributor.author | Shiue, Chyng-Yann | en_US |
dc.contributor.author | RUOH-FANG YEN | en_US |
dc.contributor.author | LING-WEI HSIN | en_US |
dc.creator | Shih, Kai-Ting;Huang, Ya-Yao;Yang, Chia-Ying;Mei-Fang Cheng;Tien, Yu-Wen;Shiue, Chyng-Yann;Yen, Rouh-Fang;Hsin, Ling-Wei | - |
dc.date.accessioned | 2021-03-22T08:47:49Z | - |
dc.date.available | 2021-03-22T08:47:49Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/554381 | - |
dc.description.abstract | (4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is a positron emission tomography (PET) imaging agent for measuring the system xC- transporter activity. It has been used for the detection of various cancers and metastasis in clinical trials. [18F]FSPG is also a promising diagnostic tool for evaluation of multiple sclerosis, drug resistance in chemotherapy, inflammatory brain diseases, and infectious lesions. Due to the very short half-life (110 min) of 18F nuclide, [18F]FSPG needs to be produced on a daily basis; therefore, fast and efficient synthesis and analytical methods for quality control must be established to assure the quality and safety of [18F]FSPG for clinical use. To manufacture cGMP-compliant [18F]FSPG, all four nonradioactive stereoisomers of FSPG were prepared as reference standards for analysis. (2S,4S)-1 and (2R,4R)-1 were synthesized starting from protected L- and D-glutamate derivatives in three steps, whereas (2S,4R)-1 and (2R,4S)-1 were prepared in three steps from protected (S)- and (R)-pyroglutamates. A chiral HPLC method for simultaneous determination of four FSPG stereoisomers was developed by using a 3-cm Chirex 3126 column and a MeCN/CuSO4(aq) mobile phase. In this method, (2R,4S)-1, (2S,4S)-1, (2R,4R)-1, and (2S,4R)-1 were eluted in sequence with sufficient resolution in less than 25 min without derivatization. Scale-up synthesis of intermediates for the production of [18F]FSPG in high optical purity was achieved via stereo-selective synthesis or resolution by recrystallization. The enantiomeric excess of intermediates was determined by HPLC using a Chiralcel OD column and monitored at 220 nm. The nonradioactive precursor with >98% ee can be readily distributed to other facilities for the production of [18F]FSPG. Based on the above accomplishments, cGMP-compliant [18F]FSPG met the acceptance criteria in specifications and was successfully manufactured for human use. It has been routinely prepared and used in several pancreatic ductal adenocarcinoma metastasis-related clinical trials. | en_US |
dc.language.iso | animation | en_US |
dc.relation.ispartof | PloS one | en_US |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | florilglutamic acid; florilglutamic acid f 18; 4-(3-fluoropropyl)glutamic acid; glutamic acid derivative; Article; carbon nuclear magnetic resonance; crystallization; drug purity; drug structure; drug synthesis; high performance liquid chromatography; proton nuclear magnetic resonance; scale up; standard; stereoisomerism; chemistry; human; injection; stereoisomerism; synthesis; Chromatography, High Pressure Liquid; Crystallization; Glutamates; Humans; Injections; Stereoisomerism | - |
dc.title | Synthesis and analysis of 4-(3-fluoropropyl)-glutamic acid stereoisomers to determine the stereochemical purity of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) for clinical use | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1371/journal.pone.0243831 | - |
dc.identifier.pmid | 33315962 | - |
dc.identifier.scopus | 2-s2.0-85098329426 | - |
dc.identifier.url | https://scholars.lib.ntu.edu.tw/handle/123456789/541363 | - |
dc.relation.journalvolume | 15 | en_US |
dc.relation.journalissue | 12 | en_US |
item.languageiso639-1 | animation | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
crisitem.author.dept | Radiology | - |
crisitem.author.dept | Nuclear Medicine-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Radiology | - |
crisitem.author.dept | Nuclear Medicine-NTUH | - |
crisitem.author.dept | Pharmacy | - |
crisitem.author.dept | School of Pharmacy | - |
crisitem.author.orcid | 0000-0002-9359-0606 | - |
crisitem.author.orcid | 0000-0002-9126-2705 | - |
crisitem.author.orcid | 0000-0003-1648-6482 | - |
crisitem.author.orcid | 0000-0001-5018-4491 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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