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W. Yu et al. / Bioorg. Med. Chem. Lett. 18 (2008) 1264–1268
The uptake of radioactivity of [18F] labeled anti-FAC-
BC,2 syn-FMACBC3, and anti-FMACBC3 in tumors
at 60 min p.i. were 1.72, 1.59, and 2.50% ID/g in the
same animal model, respectively, which resulted in tu-
mor to brain ratios of 6.6:1, 6.9:1 and 8.9:1, respec-
tively.2,3 Thus, the characteristics of candidate
compounds 16, 17, and 18 are comparable with anti-
FACBC, syn-FMACBC, and anti-FMACBC, by enter-
ing 9L cells via L-type transport system in vitro and
showing high levels of uptake in 9L brain tumors
in vivo in comparison to normal brain.
studies. Research supported by Nihon Medi-Physics
Co., Ltd.
References and notes
1. McConathy, J.; Voll, R. J.; Yu, W.; Crowe, R. J.;
Goodman, M. M. Appl. Radiat. Isot. 2003, 58, 657.
2. Shoup, T. M.; Olson, J.; Hoffman, J. M.; Votaw, J.;
Eshima, D.; Eshima, L.; Camp, V. M.; Stabin, M.; Votaw,
D.; Goodman, M. M. J. Nucl. Med. 1999, 40, 331.
3. Martarello, L.; McConathy, J.; Camp, V. M.; Malveaux,
E. J.; Simpson, N. E.; Simpson, C. P.; Olson, J. J.; Bowers,
G. D.; Goodman, M. M. J. Med. Chem. 2002, 45, 2250.
4. Nye, J. A.; Schuster, D. M.; Yu, W.; Camp, V. M.;
Goodman, M. M.; Votaw, J. R. J. Nucl. Med. 2007, 48,
1017.
5. Oka, S.; Hattori, R.; Kurosaki, F.; Toyama, M.; Williams,
L. A.; Yu, W.; Votaw, J. R.; Yoshida, Y.; Goodman, M.
M.; Ito, O. J. Nucl. Med. 2007, 48, 46.
6. Schuster, D. M.; Votaw, J. R.; Nieh, P. T.; Yu, W.; Nye, J.
A.; Master, V.; Bowman, F. D.; Issa, M. M.; Goodman,
M. M. J. Nucl. Med. 2007, 48, 56.
In summary, three new SPECT tumor imaging agents,
syn-, anti-, and gem-IVACBC 16, 17, and 18 have been
synthesized, [123I] labeled and biologically evaluated.
All these compounds demonstrated high levels of tumor
uptake in vitro and in vivo in a 9L rat gliosarcoma brain
tumor model and they are L-type amino acid trans-
porter substrates. These results are comparable with
those of anti-FACBC, syn-FMACBC, and anti-
FMACBC in the same animal model, which support
the candidacy of syn-, anti-, and gem-IVACBC 16, 17,
and 18 as promising SPECT brain tumor imaging
agents.
7. Jager, P. L.; Vaalburg, W.; Pruim, J.; de Vries, E. G.;
Langen, K. J.; Piers, D. A. J. Nucl. Med. 2001, 42, 432.
8. Mancuso, A. J.; Swern, D. Synthesis 1981, 3, 165.
9. Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986,
108, 7408.
10. De Lera, A. R.; Torrado, A.; Iglesias, B.; Lopez, S.
Tetrahedron Lett. 1992, 33, 6205.
Acknowledgments
11. Wulff, W. D.; Powers, T. S. J. Org. Chem. 1993, 58, 2381.
12. Yu, W.; McConathy, J.; Olson, J. J.; Camp, V. M.;
Goodman, M. M. J. Med. Chem. 2007, 50, 6718.
13. Panekand, J. S.; Jain, N. F. J. Org. Chem. 2001, 66, 2747.
We are grateful to Dr. Bing Wang of the NMR Center
of Emory University for his assistance with NMR stud-
ies and Zhaobin Zhang for his assistance with the in vivo