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@INPROCEEDINGS{Schfer:825270,
author = {Schäfer, Dominique and Weiss, Philipp and Castillo, Johnny
and Ermert, Johannes and Coenen, Heinrich Hubert},
title = {{A} new method for the two-step synthesis of n.c.a.
6-[{F}-18]fluorotryptophan},
reportid = {FZJ-2016-07741},
year = {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.},
month = {May},
date = {2015-05-26},
organization = {21st International Symposium on
Radiopharmaceutical Sciences, Columbia
(USA), 26 May 2015 - 31 May 2015},
subtyp = {Plenary/Keynote},
cin = {INM-5},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {572 - (Dys-)function and Plasticity (POF3-572)},
pid = {G:(DE-HGF)POF3-572},
typ = {PUB:(DE-HGF)24},
url = {https://juser.fz-juelich.de/record/825270},
}