Production at the Curie level of no-carrier-added 6-18F-fluoro-L-dopa.

UNLABELLED: 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). CONCLUSION: 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.

Metabolism of no-carrier-added 2-[18F]fluoro-L-tyrosine in rats.

BACKGROUND: Several fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among these, 2-[18F]fluoro-L-tyrosine (2-[18F]Tyr) has been studied in mice at a low specific activity. Its incorporation into proteins is fast and metabolism via other pathways is limited. The present in vivo study was carried out in normal awake rats using no-carrier-added 2-[18F]Tyr. Under normal physiological conditions, we have studied the incorporation into proteins and the metabolism of the tracer in different brain areas. METHODS: No-carrier-added 2-[18F]Tyr was administered to awake rats equipped with chronic arterial and venous catheters. The time course of the plasma activity was studied by arterial blood sampling. The biodistribution of the activity in the main organs was studied at the end of the experiment. The distribution of radioactive species in plasma and brain regions was studied by acidic precipitation of the proteins and HPLC analysis of the supernatant. RESULTS: The absolute uptake of radioactivity in brain regions was homogenous. In awake rats, no-carrier-added 2-[18F]Tyr exhibits a fast and almost quantitative incorporation into the proteins fractions of cerebellum and cortex. In striatum, this incorporation into proteins and the unchanged fraction of the tracer detected by HPLC could be lower than in other brain regions. CONCLUSION: This study confirms the potential of 2-[18F]fluoro-L-tyrosine as a tracer for the assessment of the rate of protein synthesis by positron emission tomography. The observed metabolism suggests a need for a correction for the appearance of metabolites, at least in plasma.