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Optimization of 18 F‐syntheses using 19 F‐reagents at tracer‐level concentrations and liquid chromatography/tandem mass spectrometry analysis: Improved synthesis of [ 18 F]MDL100907
Author(s) -
Zhang Xiang,
Dunlow Ryan,
Blackman Burchelle N.,
Swenson Rolf E.
Publication year - 2018
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3606
Subject(s) - radiosynthesis , chemistry , tracer , reagent , yield (engineering) , radiochemistry , tandem , mass spectrometry , chromatography , analytical chemistry (journal) , nuclear physics , nuclear medicine , organic chemistry , positron emission tomography , medicine , physics , materials science , metallurgy , composite material
Traditional radiosynthetic optimization faces the challenges of high radiation exposure, cost, and inability to perform serial reactions due to tracer decay. To accelerate tracer development, we have developed a strategy to simulate radioactive 18 F‐syntheses by using tracer‐level (nanomolar) non‐radioactive 19 F‐reagents and LC‐MS/MS analysis. The methodology was validated with fallypride synthesis under tracer‐level 19 F‐conditions, which showed reproducible and comparable results with radiosynthesis, and proved the feasibility of this process. Using this approach, the synthesis of [ 18 F]MDL100907 was optimized under 19 F‐conditions with greatly improved yield. The best conditions were successfully transferred to radiosynthesis. A radiochemical yield of 19% to 22% was achieved with the radiochemical purity >99% and the molar activity 38.8 to 53.6 GBq/ μmol ( n = 3). The tracer‐level 19 F‐approach provides a high‐throughput and cost‐effective process to optimize radiosynthesis with reduced radiation exposure. This new method allows medicinal and synthetic chemists to optimize radiolabeling conditions without the need to use radioactivity.