Automated production of [¹⁸F]FTHA according to GMP

Abstract

14-(R,S)-[ 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 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)-[ 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)-[ 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.

Clinical translation of 18F-fluoropivalate – a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers

“…Perhaps the most promising long chain fatty acid analogue is 14(R,S)-18 F-fluoro-6-thia-heptadecanoic acid ( 18 F-FTHA) [27,28]. GMP production of this tracer was achieved in a good radiochemical yield of 13% [29]. Clinical studies are yet to be reported.…”

Basal and cold-induced fatty acid uptake of human brown adipose tissue is impaired in obesity

“…10 min), an intravenous injection of 18 F-FTHA was given and a dynamic emission scan was performed (frames: 1 × 60 s, 6 × 30 s, 1 × 60 s, 3 × 300 s, 2 × 600 s) on the same area as with radiowater. 18 F-FTHA was produced as previously described 33 , 34 .…”

Radiosynthesis of the norepinephrine transporter tracer [18F]NS12137 via copper‐mediated 18F‐labelling

“…[ 18 F]Fluoride was produced as reported previously . The initial amount of [ 18 F]F − used was 6.4 ± 2.5 GBq in the radiochemistry studies and 16.4 ± 1.5 GBq for A m determinations.…”

“…[ 18 F]Fluoride was produced as reported previously. 22 The initial amount of [ 18 F]F − used was 6.4 ± 2.5 GBq in the radiochemistry studies and 16.4 ± 1.5 GBq for A m determinations. The [ 18 F]KF solution was dried using azeotropic distillation with MeCN and Kryptofix K 222 (15.5-16.5 μmol) at 120°C with helium flow to form the dry [ 18 F]KF/K 222 complex.…”