Optimization of 18F-Syntheses using 19F-Reagents at Tracer-level Concentrations and LC-MS/MS Analysis: Improved Synthesis of [18F]MDL100907

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 61; no. 5; pp. 427 - 437
• Main Authors: Zhang, Xiang, Dunlow, Ryan, Blackman, Burchelle N., Swenson, Rolf E.
• Format: Journal Article
• Language: English
• Published: 17.04.2018
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3606

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 19–22% was achieved with the radiochemical purity >99% and the molar activity 38.8 – 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. A strategy to simulate radioactive 18 F-syntheses with non-radioactive 19 F-reagents was developed. Reaction optimization was performed with tracer-level (nanomolar) 19 F-reagents and analyzed by high-throughput screening with LC-MS/MS. The best conditions were then transferred to 18 F-radiosynthesis. This approach provides a high-throughput and cost-effective process to optimize radiosyntheses with reduced radiation exposure.