Automated production of [18F]FTHA according to GMP. (22nd February 2018)

• Record Type: Journal Article
• Authors: Savisto, Nina; Viljanen, Tapio; Kokkomäki, Esa; Bergman, Jörgen; Solin, Olof
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 61:Number 2(2018)
• Page Start: 84
• Page End: 93
• Publication Date: 2018-02-22
• Subjects: [18F]FTHA -- 18F‐fluoride -- automation -- fatty acid metabolism -- process validation -- radiosynthesis; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3589
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : 14‐( R, S )‐[ 18 F]fluoro‐6‐thia‐heptadecanoic acid is a tracer for fatty acid imaging by positron emission tomography. High demand for this tracer required us to replace semiautomatic synthesis with a fully automated procedure. An automated synthesis device was constructed in‐house for multistep nucleophilic 18 F‐fluorination and a control system was developed. The synthesis device was combined with a sterile filtration unit and both were qualified. 14‐( R, S )‐[ 18 F]fluoro‐6‐thia‐heptadecanoic acid was produced according to good manufacturing practice guidelines set by the European Union. The synthesis includes an initial nucleophilic labelling reaction, deprotection, preparative HPLC separation, purification of the final product, and formulation for injection. The duration and temperature of the reaction and hydrolysis were optimized, and the radiochemical stability of the formulated product was determined. The rotary evaporator used to evaporate the solvent after HPLC purification was replaced with solid phase extraction purification. We also replaced the human serum albumin used in the earlier procedure with a phosphate buffer‐ascorbic acid mixture in the final formulation solution. From 2011 to 2016, we performed 219 synthesis procedures, 94% of which were successful. The radiochemical yield of 14‐( R, S )‐[ 18 F]fluoro‐6‐thia‐heptadecanoic acid, decay‐corrected to the end of bombardment, was 13% ± 6.3%. The total amount of formulated end product was 1.7 ± 0.8 GBq at end of synthesis. Abstract : A procedure for the radiosynthesis of 14‐( R, S )‐[ 18 F]fluoro‐6‐thia‐heptadecanoic acid that meets the requirements of regulatory bodies and is intended for clinical use was established. An automated synthesis device suitable for multistep nucleophilic labelling was constructed and a control system was developed. The process is user‐friendly and good manufacturing practice compliant, providing a sufficient amount of 14‐( R, S )‐[ 18 F]fluoro‐6‐thia‐heptadecanoic acid for multiple clinical studies.