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. 2017;1(1):7.
doi: 10.1186/s41181-016-0009-1. Epub 2016 Apr 4.

Improved GMP-compliant multi-dose production and quality control of 6-[18F]fluoro-L-DOPA

G Luurtsema  1 , H H Boersma  1 , M Schepers  1 , A M T de Vries  1 , B Maas  1 , R Zijlma  1 , E F J de Vries  1 , P H Elsinga  1
Affiliations

Improved GMP-compliant multi-dose production and quality control of 6-[18F]fluoro-L-DOPA

G Luurtsema et al. EJNMMI Radiopharm Chem. 2017.

Erratum in

Abstract

Background: 6-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) is a frequently used radiopharmaceutical for detecting neuroendocrine and brain tumors and for the differential diagnosis of Parkinson's disease. To meet the demand for FDOPA, a high-yield GMP-compliant production method is required. Therefore, this study aimed to improve the FDOPA production and quality control procedures to enable distribution of the radiopharmaceutical over distances.FDOPA was prepared by electrophilic fluorination of the trimethylstannyl precursor with [18F]F2, produced from [18O]2 via the double-shoot approach, leading to FDOPA with higher specific activity as compared to FDOPA which was synthesized, using [18F]F2 produced from 20Ne, leading to FDOPA with a lower specific activity. The quality control of the product was performed using a validated UPLC system and compared with quality control with a conventional HPLC system. Impurities were identified using UPLC-MS.

Results: The [18O]2 double-shoot radionuclide production method yielded significantly more [18F]F2 with less carrier F2 than the conventional method starting from 20Ne. After adjustment of radiolabeling parameters substantially higher amounts of FDOPA with higher specific activity could be obtained. Quality control by UPLC was much faster and detected more side-products than HPLC. UPLC-MS showed that the most important side-product was FDOPA-quinone, rather than 6-hydroxydopa as suggested by the European Pharmacopoeia.

Conclusion: The production and quality control of FDOPA were significantly improved by introducing the [18O]2 double-shoot radionuclide production method, and product analysis by UPLC, respectively. As a result, FDOPA is now routinely available for clinical practice and for distribution over distances.

Keywords: Automation; PET; Quality control; Radiochemistry; Radionuclide production.

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Figures

Fig. 1
Fig. 1
A schematic overview of FDOPA synthesis module including HPLC purification, collection of the end product and filter integrity test
Fig. 2
Fig. 2
Synthesis of 18F-FDOPA
Fig. 3
Fig. 3
An example of a typical chromatogram of FDOPA -L performed with UPLC-UV and radioactivity detector (upper). Green is UV and the black line is RA signal. Notice that because the different detector position there is a delay in RA-signal. Below, a typical presentation of a chromatogram of FDOPA -L performed with HPLC-UV and radioactivity detector
Fig. 4
Fig. 4
a Mass spectra of low specific activity FDOPA sample. No 6-hydroxy-DOPA was found in the sample (above). Peak of FDOPA-quinone (middle) was detected and the total ion current chromatogram is presented below. b Proposed FDOPA- quinone fragments
See this image and copyright information in PMC

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