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n.c.a. [¹⁸F]FDOPA from [¹⁸F]fluoride using nucleophilic aromatic substitution

¹ Radiopharmacy, University Hospital Tuebingen, Tuebingen, Germany

1260

Objectives: 6-[¹⁸F]Fluoro-L-DOPA is well known as PET biomarker of clinical importance. Commonly, this tracer is synthesized applying electrophilic fluorination with [¹⁸F]F₂ to yield the c.a. product. Taking into account the advantages of the production of [¹⁸F]fluoride, nucleophilic fluorination in the synthesis of [¹⁸F]FDOPA is desirable. Here, we report modifications and optimizations on the Lemaire synthesis (1) to improve yield and reliability of the nucleophilic [¹⁸F]FDOPA synthesis in an in-house developed automated synthesizer.

Methods: [¹⁸F]FDOPA was prepared in 4 steps: a) ¹⁸F-fluorination of 4,5-dimethoxy-2-nitrobenzaldehyde (5mg, 1mL DMF, 140°C, K¹⁸F/K2.2.2.); purification (C18, ALN cartridges); b) iodination (diiodosilane, r.t.); c) alkylation (CH₂Cl₂, r.t., 10min, phasetransfer catalyst, CsOH, N-(diphenylmethylene)-glycine tert-butyl ester); d) deprotection (48% HBr, KI, 150°C, 10 min). After neutralization, the product was isolated by RP-HPLC.

Results: [¹⁸F]FDOPA was obtained (n = 5) in a yield of 9064 ± 3076 MBq (Irradiation: 120 min; 35 µA). Radiochemical purity was 95 %, specific activity ca. 50 GBq/µmol at EOS and enantiomeric purity ee 95 %. 7 h from EOS radiochemical purity of [¹⁸F]FDOPA was > 90 %. Modifications and optimizations of the synthesis in detail: For fluorination, DMF and carbon glass vessels were used instead of DMSO and glass vessels ((2); RCY1 71%±4%); for iodination, diiodosilane was prepared directly before synthesis (RCY2 78%±4%). For hydrolysis HBr and KI were used (instead of HI; (1)); RCY4 76%±8%.

Conclusions: N.c.a. [¹⁸F]FDOPA could be synthesized reliably in high yields, in a 4-step process including nucleophilic aromatic substitution with [¹⁸F]fluoride. Ref.: (1) Lemaire et al., Eur. J. Org. Chem. 2004, 2899. (2) Al-Labadi et al., Radiochim. Acta 94, 2006, 143.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Shen, B. Articles by Machulla, H.-J. PubMed Articles by Shen, B. Articles by Machulla, H.-J.