title: Production at the Curie level of no-carrier-added 6-18F-fluoro-L-dopa.
abstract: 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) has proven to be a useful radiopharmaceutical for the evaluation of presynaptic dopaminergic function using PET. In comparison to electrophilic synthesis, the no-carrier-added (NCA) nucleophilic method has several advantages. These include much higher available activity and specific activity. Recently, we have described an NCA enantioselective synthesis using a chiral phase-transfer catalyst. However, some chemicals were difficult to implement into a commercially available synthesizer, restricting access to this radiopharmaceutical to only a few PET centers.
  
  
  METHODS
  In this paper, 2 important chemical improvements are proposed to simplify production of (18)F-FDOPA, resulting in straightforward automation of the synthesis in a commercially available module.
  
  
  RESULTS
  First, a fast, simple, and reliable synthesis of 2-(18)F-fluoro-4,5-dimethoxybenzyl iodide on a solid-phase support was developed. Second, a phase-transfer catalyst alkylation of a glycine derivative at room temperature was used to enable enantioselective carbon-carbon bond formation. After hydrolysis and high-performance liquid chromatography purification, a high enantiomeric excess of (18)F-FDOPA (≈ 97%) was obtained using a chiral catalyst available from a biphenyl 3 substrate. The total synthesis time was 63 min, and the decay-corrected radiochemical yield was 36% ± 3% (n = 8).
  
  
  CONCLUSIONS
  By exploiting the advantages of this NCA approach, using a starting activity of 185 GBq of NCA (18)F-fluoride, high activities of (18)F-FDOPA (>45 GBq) with high specific activity (≥ 753 GBq/μmol) are now available at the end of synthesis for use in clinical investigations.
authors: Cyclotron Research Center, Université de Liège, Liège, Belgium.
authors: Lionel C
authors: LC
authors: Libert
authors: Xavier
authors: X
authors: Franci
authors: Alain R
authors: AR
authors: Plenevaux
authors: Takashi
authors: T
authors: Ooi
authors: Keiji
authors: K
authors: Maruoka
authors: André J
authors: AJ
authors: Luxen
authors: Christian F
authors: CF
authors: Lemaire
mesh_terms: D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification; D007553:Isotope Labeling / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000302:isolation & purification*
chemical_list: D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine
keywords: 18F-FDOPA; 18F-fluoride; SPE; enantioselective; phase-transfer catalysis