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| Home > Publications database > A new method for the two-step synthesis of n.c.a. 6-[F-18]fluorotryptophan |
| Poster (Plenary/Keynote) | FZJ-2016-07741 |
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2015
Abstract: Objectives: Tryptophan was recently described as a possible radiotracer for tumors diagnostics1,2. Furthermore the amino acid is the precursor of serotonin biosynthesis and acts as a part in neuronal functions which seems to be inhibited by fluorinated tryptophan3. Earlier approaches using the Balz-Schiemann reaction yielded [18F]fluorotryptophan in low radiochemical yields (RCY). Newer approaches as the isotopic exchange in the carbonyl activated aromatic system with subsequent Baeyer-Villiger oxidation required three radiosynthetic steps and [18F]fluorotryptophan in carrier-added form. The aim of this work was to develop a two-step synthesis of n.c.a. 6-[18F]fluorotryptophan with high RCY.Methods: The concept of radiosynthesis is illustrated in figure 1. The precursor 2 for 6-[18F]fluorotryptophan was prepared from 6-bromo-indole. The precursor includes the Schöllkopf’s amino acid auxiliary and a boronic ester group at the desired position in the aromatic ring. The radiosynthesis was performed by a novel copper(II) mediated 18F-fluorination4 and a subsequent hydrolysis as a two-step reaction. Figure 1: Pathway to 6-[18F]fluorotryptophan 3 starting from 6-bromo indole 1 (PG = protecting group).Results: Preparation of the precursor was accomplished in a linear six-step synthesis with an overall yield of 23 %. The following n.c.a. 18F-fluorination, performed under modified conditions of the [Cu(OTf)2(py)4] mediated n.c.a. 18F-fluorination4 gave radiochemical yields of 60-65 %. After separating the product, an acidic hydrolysis was performed with about 20 % RCY. Finally L-6-[18F]fluorotryptophan was purified by HPLC with an overall RCY of about 8 % and a molar activity of XX MBq/mmol within 95 min total reaction time.Conclusions: The radiosynthesis of n.c.a. L-6-[18F]fluorotryptophan was performed in a short two-step synthesis. The radiotracer is selectively labeled in 6-position and has a high molar activity. Therefore it can be used for neuronal studies without inhibitional effects. References: [1] J. Lin et al., J. Membrain Biol. 1988, 104, 1, [2] G.C. Prendergast, Nature 2011, 478, 192, [3] C. Jacquot et al., Biochem. Pharm., 1992, 45, 1049, [4] V. Gouverneur et al., Angew. Chem. 2014, 53, 7751.
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