54
C. Lemaire et al. / Journal of Fluorine Chemistry 138 (2012) 48–55
through the cartridge. For the subsequent halogenation step, the
activity was kept on the support. For analytical purposes, the
support was washed with water (5 mL) and the benzyl alcohol
eluted from the tC18 cartridge with 2 mL of CH3CN. TLC and HPLC
analyses indicated that the reduction was near quantitative (>95%)
for all compounds.
aqueous solution of sodium formate at pH 4 (about 2 mL, the pH of
the last drop should be around 4) and then flushed with nitrogen
for 1 min. Azide synthesis on the cartridge was then realized by
passing a saturated aqueous solution of sodium azide (2 mL)
through the tC18 support. After heating for 5 min at 60 8C, excess
reagent was removed by flushing the SPE support with nitrogen for
2 min. Finally, the 2 and 4-[18F]fluorobenzyl azides (17) and (18)
were eluted with 2.5 mL of CH3CN and analysed by HPLC on a X-
4.3.3. Halogenation step
TERRA RP-C18 column (5
m
m, 150 mm ꢃ 3.9 mm) with a mixture
4.3.3.1. Procedure A. For the on-column halogenation of the benzyl
alcohol to the benzyl halides, 0.5–0.8 mL of an aqueous solution of
HCl (37%), HBr (48%) or HI (57%) were slowly passed through the
support (1–2 min). For compounds 12–15 (X = Cl, Br, I), the
reaction was conducted at RT and for compounds 10–11 and 16 the
cartridge was heated by hot air stream from an air dryer at a
controlled temperature of 60–65 8C. After reaction, the Sep-Pak1
was flushed with nitrogen for 1 min and the [18F]fluorobenzyl
halide derivatives were directly eluted with an organic solvent
such as CH3CN, dichloromethane or toluene (3 mL). For com-
pounds 12–15, the residual inorganic acid was removed by passing
the solution through a small ‘‘home-made’’ potassium carbonate
column (1.5 g). For compounds 10–11 and 16, this cartridge was
substituted with a sodium formate cartridge (1.5 g) and an
additional commercial Na2SO4 cartridge. The [18F]fluorobenzyl
halides 10–16 were then eluted from the SPE and recovered in
about 2.5 mL of an organic solvent (i.e. toluene, DCM, ether). The
radiochemical yield and purity of the different products were
determined by radio TLC and HPLC as described above (Table 2).
consisting of CH3CN water (50/50) at a flow rate of 1 mL/min (Rt
17 = 8.8 min.; Rt 11 = 10.1 min., Rt 18 = 8.7 min). Radiochemical
purity, determined by TLC analysis (Rf 17 = 0.92; Rf 18 = 0.9
(CH2Cl2/AcOEt 90/10)) was above 65%. Radiochemical yields for
the 2- and 4-[18F]fluorobenzyl azide compounds (17 and 18) were
30 and 55%, respectively.
4.4. Determination of radiochemical labeling yield
After labeling, the Me2SO solution was withdrawn from the
reaction vessel and transferred into a second glass vial. Residual
activity in the reaction vessel and the activity transferred (Activity
in solution) were counted and corrected for decay. For the
determination of the radiochemical yield, TLC and HPLC samples
(1–2
mL) withdrawn from the vial containing the activity in
solution, were diluted with a small amount of CH3CN. Radiochem-
ical purities were then determined by TLC analysis. Decay
corrected (d.c.) radiochemical yields (RCY) were obtained from
the activity trapped on the QMA support according to the following
equation:
4.3.3.2. Procedure B (For compounds 10, 11 and 16). For the RT on-
column bromination of the benzyl alcohol to the benzyl bromide 10–
11 and 16, the previously labeled aldehyde was trapped on a tC18
cartridge (1 g) connected to an oasis HLB cartridge (400 mg). After
reduction, as described above, 0.5–0.8 mL of hydrobromic acid in
acetic acid (33%) was slowly passed through the two SPE cartridges.
After 2–3 min of reaction at room temperature (RT), the support was
slowly washed with 2 mL of an aqueous solution of sodium formate
at pH 4 and then flushed with nitrogen for 1 min. During this
washing, part of the activity trapped on the tC18 cartridge was eluted
and trapped on the oasis HLB support. The [18F]fluorobenzyl bromide
derivatives 10, 11 and 16 were then directly eluted with an organic
solvent such as dichloromethane or toluene (3 mL) through three
additional commercial Na2SO4 drying cartridges.
RCY ðd:c:Þ ¼
½Activity in solution ðd:c:Þ ꢃ TLC radiochemical purity ð%Þꢄ
Activity on QMA ðd:c:Þ
Acknowledgements
´
`
This work was supported by Universite de Liege and GE grants.
A.P. is a research associate of FNRS Belgium. We would like to thank
the cyclotron operators J.-L. Genon and P. Hawotte for providing us
with fluorine-18.
The 2 and 4-[18F]fluorobenzyl bromides (10–11) and 16 were
then recovered in 2–2.5 mL of toluene or dichloromethane. The
radiochemical yield and purity of these compounds was deter-
mined by radio-TLC and radio-HPLC analyses as described above.
The sodium formate solution was prepared by dissolving 13.6 g
of this salt in 50 mL of water. The pH of the solution was then
adjusted to 4 with HCl (37%).
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4.3.4.1. Via HBr 48% or HI 57%. Synthesis of 2 and 4-[18F]fluorobenzyl
halides (10–11, X = Br, I) was realized with HBr (48%) or HI (57%) as
described in procedure A (Section 4.3.3.1). After reaction, the Sep-
Pak1 was washed with an aqueous solution of sodium formate at pH
4 and the azide synthesis realized on the same cartridge as described
above (Section 4.3.4.1). Via the HBr and the HI pathway, the
radiochemical yield of 2-[18F]fluorobenzyl azide (17) was 56% and
57%, respectively. Via these two different acids, radiochemical yield
of 4-[18F]fluorobenzyl azide (18) was around 60%.
4.3.4.2. Via HBr/HOAc 33%. Synthesis of 2 and 4-[18F]fluorobenzyl
bromides (10 and 11) was realized as described in procedure B
(Section 4.3.3.2). After reaction, the Sep-Pak1 was washed with an