Robotic synthesis of 6-[18F]fluoro-L-dopa

Abstract

The aim of this study was to develop a method of semi-automated 6-[18F]fluoro-L-dopa (6-[18F]FDOPA) synthesis using a robotic system (Scanditronix Anatech RB III, Uppsala, Sweden). [18F]Fluorine was produced via 20Ne(d,alpha)18F using a Scanditronix MC17F cyclotron (Uppsala). The radiosynthesis was performed by the Scanditronix Anatech RB III robotic system. On average, a typical run produced 16-19 mCi of 6-[18F]FDOPA at end of synthesis (EOS) after 2 h irradiation of the F2/neon gas target. The total synthesis time was 110 min. The retention time of 6-[18F]FDOPA (the radio peak) was 8.2 min, which was consistent with the 6-[19F]FDOPA ultraviolet peak. The radiochemical purity was greater than 97%. A robotic, semi-automated method for 6-[18F]FDOPA radiosynthesis is therefore feasible. The radiation burden for the operator can be reduced as much as possible. Sufficient activity of 6-[18F]FDOPA could be obtained for positron emission tomography studies of dopaminergic function.

Electrophilic synthesis of 6-[18F]fluoro-L-DOPA using post-target produced [18F]F2

“…Protecting groups were hydrolyzed with HBr as in previous studies [7,8,10,15], but less HBr was used and hydrolysis time was reduced by half. After neutralization, the volume of the reaction mixture was only 700 µL, small enough for the optimal resolution of FDOPA from L-DOPA in semi-preparative purification.…”

“…In this automated system, the protected intermediate is used without further purification and the final semi-preparative purification is modified. In addition to the method of de Vries et al, other laboratories have utilized fluorodestannylation in order to produce [ 18 F]FDOPA [8,15,16]. We herein present our semi-automated modification of Namavari's method [7] …”

Evaluation of Inhibitory Effect of Recreational Drugs on Dopaminergic Terminal Neuron by PET and Whole-Body Autoradiography

“…[ 18 F]FDOPA synthesis was performed by use of a previously reported procedure [21]. The radiochemical purity was greater than 97% the chemical and radiochemical purities of the product isolated from the semipreparative high-pressure liquid chromatography system that were further confirmed by an analytic high-pressure liquid chromatography method (specific activity ∼18.5 ×  10 10  Bq/mmol (5 Ci/mmol)) and were both greater than 99%.…”

GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP “Fluorodopa F 18 Injection”

“…Nevertheless, the specific activity for the clinical application of FDOPA does not seem to be an limiting factor, because the molecular targets of FDOPA are either aromatic amino acid decarboxylase or large amino acid transporter, both being large capacity targets. Methods for the FDOPA production by either programcontrolled automatic synthesis module or robotic system were also reported and both resulted in very similar yield and requiring similar amount of time for the procedures [9,10]. The choice of the production method is, therefore, depending on the manufacturer's preference.…”