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Figure 4. Ex vivo autoradiograms in AMPA lesioned rat brains of: (a) [18F]15 (6-
[
[
18F]fluoro-PBR28, control), (b) 18F]15 + 15, (c) 18F]15 + PK11195 and (d)
[ [
18F]15 + flumazenil.
27. Wilson, A. A.; Garcia, A.; Parkes, J.; McCormick, P.; Stephenson, K. A.; Houle, S.;
Vasdev, N. Nucl. Med. Biol. 2008, 35, 308.
28. Dollé, F. Curr. Pharm. Design 2005, 11, 3221.
gand, [11C]PK11195, displayed a rapid clearance in the same
region.
29. Makosza, M.; Sienkiewicz, K. J. Org. Chem. 1998, 63, 4199.
Ex vivo binding experiments were also performed with [18F]15
as depicted in Figure 4: autoradiography on brain sections resulted
in a high ipsi- to controlateral ratio, which was abolished by an ex-
cess (20 nM) of non-radioactive 15 or PK11195 but not flumazenil.
In conclusion, 6-fluoro-PBR28 (15), a fluorinated analogue of
the TSPO ligand PBR28, was synthesized and labelled with fluo-
rine-18. The discussed biological evaluation studies demonstrate
the potential of this radiofluorinated tracer to image in vivo the
TSPO using PET.
30. Stavenger, R. A.; Cui, H.; Dowdell, S. E.; Franz, R. G.; Gaitanopoulos, D. E.;
Goodman, K. B.; Hilfiker, M. A.; Ivy, R. L.; Leber, J. D.; Marino, Jr. J. P.; Oh, H.-J.;
Viet, A. Q.; Xu, W.; Ye, G.; Zhang, D.; Zhao, Y.; Jolivette, L. J.; Head, M. S.; Semus,
S. F.; Elkins, P. A.; Kirkpatrick, R. B.; Dul, E.; Khandekar, S. S.; Yi, T.; Jung, D. K.;
Wright, L. L.; Smith, G. K.; Behm, D. J.; Doe, C. P.; Bentley, R.; Chen, Z. X.; Hu, E.;
Lee, D. J. Med. Chem. 2007, 50, 2.
31. Okubo, T.; Yoshikawa, R.; Chaki, S.; Okuyama, S.; Nakazato, A. Bioorg. Med.
Chem. 2004, 12, 423.
32. Characterisation data. Compound 13: a colourless syrup, Rf = 0.14 (heptane/
EtOAc 7:3). 1H NMR (CD2Cl2): d 7.96 (s, 1H), 7.48 (t, 2H, J = 8.0 Hz), 7.34 (m,
2H), 7.27 (d, 1H, J = 8.0 Hz), 6.96 (d, 2H, J = 7.6 Hz), 6.91 (t, 1H, J = 7.2 Hz), 6.82
(d, 1H, J = 8.0 Hz), 6.56 (s, 1H), 5.10 (d, 1H, J = 14.4 Hz), 4.82 (d, 1H, J = 14.4 Hz),
3.63 (s, 3H), 1.97 (s, 3H). 13C NMR (CD2Cl2): d 170.1 [C], 162.3 [C], 157.6 [C],
152.8 [C], 151.2 [C], 150.7 [CH], 131.1 [CH], 130.4 [2CH], 129.0 [CH], 128.2 [C],
126.3 [CH], 124.6 [C], 120.7 [2CH], 120.4 [CH], 110.3 [CH], 110.2 [CH], 54.9
[CH3], 45.8 [CH2], 21.9 [CH3]. ESI(+)-FS-MS (m/z): 383/385 [M+H]+. Compound
14: a white solid, Rf = 0.15 (heptane/EtOAc 7:3). 1H NMR (CDCl3): d 7.93 (s, 1H),
7.45 (t, 2H, J = 8.0 Hz), 7.33 (m, 2H), 7.24 (m, 1H), 6.89 (m, 3H), 6.76 (d, 1H,
J = 8.0 Hz), 6.67 (s, 1H), 5.12 (d, 1H, J = 14.0 Hz), 4.84 (d, 1H, J = 14.0 Hz), 3.60 (s,
3H), 1.98 (s, 3H). 13C NMR (CD2Cl2): d 169.9 [C], 161.9 [C], 157.6 [C], 152.7 [C],
151.1 [CH], 141.3 [C], 131.1 [CH], 130.4 [2CH], 129.0 [CH], 128.6 [C], 126.3
[CH], 124.6 [C], 120.7 [2CH], 120.4 [CH], 114.0 [CH], 110.2 [CH], 54.9 [CH3],
45.8 [CH2], 22.0 [CH3]. ESI(+)-FS-MS (m/z): 427/429 [M + H]+. Compound 15: a
colourless syrup, Rf = 0.14 (heptane/EtOAc 7:3). 1H NMR (CD2Cl2): d 7.80 (s,
1H), 7.48 (t, 2H, J = 8.0 Hz), 7.34 (d, 2H, J = 8.0 Hz), 7.26 (dt, 1H, J = 7.6, 1.6 Hz),
6.97 (d, 2H, J = 8.0 Hz), 6.91 (t, 1H, J = 7.2 Hz), 6.81 (d, 1H, J = 8.0 Hz), 6.13 (d,
1H, J = 1.2 Hz), 5.11 (d, 1H, J = 14.0 Hz), 4.82 (d, 1H, J = 14.0 Hz), 3.63 (s, 3H),
1.97 (s, 3H). 13C NMR (CD2Cl2): d 170.4 [C], 164.5 [C, d, J3CÀF = 11 Hz], 163.4 [C, d,
J1CÀF = 236 Hz], 157.6 [C], 152.8 [C], 148.5 [CH, d, JC3ÀF = 19 Hz], 131.1 [CH], 130.4
[2CH], 129.0 [CH], 127.1 [C], 126.4 [CH], 124.7 [C], 120.7 [2CH], 120.3 [CH],
110.2 [CH], 95.4 [CH, d, J2CÀF = 45 Hz], 55.0 [CH3], 45.8 [CH2], 21.9 [CH3]. ESI(+)-
FS-MS (m/z): 367 [M + H]+. Anal. Calcd for: C, 68.84; H, 5.23; N, 7.65. Found: C,
68.61; H, 5.25; N, 7.59.
Acknowledgements
The authors wish to thank the cyclotron operators Mr. Daniel
Gouel, Mr. Christophe Peronne and Mr. Christophe Lechêne for per-
forming the irradiations. The authors also wish to thank Dr. Dirk
Roeda for proof reading the Letter and suggesting linguistic correc-
tions. This work was supported in part by the EC-FP6-projects DiMI
(LSHB-CT-2005-512146) and EMIL (LSH-2004-503569).
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