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C. Asakawa et al. / Bioorg. Med. Chem. Lett. 21 (2011) 7017–7020
which have high CA IX expression and MCF-7 breast tumor cells,15
which have low CA IX expression, respectively. At 15 min and
60 min after incubation with [11C]1a, the uptake level of radioac-
tivity in HT-29 cells was 1.2-fold and 1.6-fold higher than that in
MCF-7 cells, respectively. This result suggests that [11C]1a might
specifically accumulate in CA IX-rich tumor cells, although the dif-
ference in the uptake between HT-29 and MCF-7 cells was not as
high as we anticipated. Because of the short half-life of 11C, we
could not measure the uptake of [11C]1a in both tumor cell lines
until after a longer time. To achieve a greater difference in the cel-
lular uptake between the two cell lines, we will try to label 1a with
longer half-life positron emitters, such as 18F (109 min) and 124I
(4.15 d).
6. Said, H. M.; Supuran, C. T.; Hageman, C.; Staab, A.; Polat, B.; Katzer, A.;
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In conclusion, [11C]1a–c were synthesized using [11C]COCl2 as a
labeling agent, via the intermediate preparation of isocyanate
[
11C]4a–c. The labeling route was reliable and reproducible, which
guaranteed enough radioactivity of [11C]1a for in vitro and further
in vivo evaluation. We are preparing animal models bearing sev-
eral tumors and will perform PET imaging with [11C]1a for the
modeled animals. PET imaging with [11C]1a may be a useful tool
to study CA IX in the hypoxic tumors.
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called as a Kitagawa gas detection tube used to measure the CCl4 concentration
in working environment.
Acknowledgments
We are grateful to Mrs. Y. Yoshida and N. Nengaki (SHI Acceler-
ator Service Co., Ltd) for technical support with radiosynthesis. We
also thank the staff of the National Institute of Radiological Sci-
ences for support with the cyclotron operation and radionuclide
production.
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Supplementary data
25. Lemoucheux, L.; Roudlen, J.; Ibezizene, M.; Sobrio, F.; Kasne, M. C. J. Org. Chem.
2003, 68, 7289.
26. Dollé, F.; Martarello, L.; Bramoulle, Y.; Bottlaendler, M.; Gee, A. D. J. Labelled
Compd. Radiopharm. 2005, 48, 501.
Supplementary data associated with this article can be found, in
27. Fukumura, T.; Suzuki, H.; Mukai, K.; Zhang, M.-R.; Yoshida, Y.; Nemoto, K.;
Suzuki, K. J. Labellled Compd. Radiopharm. 2007, 50, S202.
28. HPLC was performed using a JASCO HPLC system (JASCO, Tokyo). Column: Capcell
Pac C18 (Shiseido, Tokyo), 10 mm ꢂ 250 mm for purification, 10 mm ꢂ 250 mm
for analysis; detector: UV 254 nM.
References and notes
1. Alterio, V.; Hilvo, M.; Di Fiore, A.; Supuran, C. T.; Pan, P.; Pakkila, S.; Scaloni, A.;
Pastorek, J.; Pastorekova, S.; Pedone, C.; Scozzafava, A.; Monti, S. M.; De Simone,
G. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 16233.
[
11C] 1a, purification: CH3CN/H2O = 40/60 (0.1% trifluoroacetic acid (TFA)),
2. Supuran, C. T. Nat. Rev. Drug Disc. 2008, 7, 168–181.
5.0 mL/min, 8.5 min; analysis: CH3CN/H2O = 40/60 (0.1% TFA), 1.0 mL/min,
8.2 min.
3. Ozensoy, O.; De Simone, G.; Supuran, C. T. Curr. Med. Chem. 2010, 17, 1516.
4. De Simone, G.; Supuran, C. T. Biochim. Biophys. Acta. 2010, 1804, 404.
5. Wykoff, C. C.; Beasley, N. J.; Watson, P. H.; Turner, K. J.; Pastorek, J.; Sibtain, A.;
Wilson, G. D.; Turley, H.; Talks, K. L.; Maxwell, P. H.; Pugh, C. W.; Ratcliffe, P. J.;
Harris, A. L. Cancer Res. 2000, 60, 7075.
[
11C] 1b, purification: CH3CN/H2O = 35/65 (0.1% TFA), 4.0 mL/min, 9.7 min;
analysis: CH3CN/H2O = 30/70 (0.1% TFA), 1.5 mL/min, 6.0 min.
11C] 1c, purification: CH3CN/H2O = 45/65 (0.1% TFA), 4.5 mL/min, 12.0 min;
analysis: CH3CN/H2O = 45/65 (0.1% TFA), 1.2 mL/min, 7.3 min.
[