In Vivo Evaluation of the Nitroimidazole-Based Thioflavin-T Derivatives as Cerebral Ischemia Markers

Chu, Taiwei; Li, Zejun; Liu, Xinqi; Wang, Xiangyun

doi:https://doi.org/10.1155/2007/49791

International Journal of Biomedical Imaging

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Recent Advances in Molecular Imaging

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Research Article | Open Access

Volume 2007 | Article ID 049791 | https://doi.org/10.1155/2007/49791

In Vivo Evaluation of the Nitroimidazole-Based Thioflavin-T Derivatives as Cerebral Ischemia Markers

Taiwei Chu,¹Zejun Li,¹Xinqi Liu,¹and Xiangyun Wang¹

Academic Editor: Wei Liang

Received10 Apr 2007

Accepted05 Jul 2007

Published28 Aug 2007

Abstract

Timely imaging and accurate interpretation of cerebral ischemia are required to identify patients who might benefit from more aggressive therapy, and nuclear medicine offers a noninvasive method for demonstrating cerebral ischemia. Three nitroimidazole-based thioflavin-T derivatives, N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl) propanamide (4NPBTA), N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl)-N-methylpropanamide (4NPBTA-1), and N-[4-(benzothiazol-2-yl)phenyl]-3-(2-nitroimidazole-1-yl) propanamide (2NPBTA), were radioiodinated and evaluated as possible cerebral ischemia markers. In normal mice, these compounds showed good permeation of the intact blood-brain barrier (BBB), high initial brain uptake, and rapid washout. In gerbil stroke models that had been subjected to right common carotid artery ligation to produce cerebral ischemia, [I131]2NPBTA, uptake in the right cerebral hemisphere decreased more slowly than that of the left, and the right/left hemisphere uptake ratios increased with time. Also, the right/left hemisphere uptake ratios correlated positively with the severity of the stroke. The results showed that [I131]2NPBTA had a specific location in the cerebral ischemic tissue. This represented a first step in finding new drugs and might provide a possible cerebral ischemic marker.

References

G. W. Petty, R. D. Brown Jr., J. P. Whisnant, J. D. Sicks, W. M. O'Fallon, and D. O. Wiebers, “Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence,” Stroke, vol. 31, no. 5, pp. 1062–1068, 2000.
View at: Google Scholar
N. J. Beauchamp Jr., P. B. Barker, P. Y. Wang, and P. C. M. vanZijl, “Imaging of acute cerebral ischemia,” Radiology, vol. 212, no. 2, pp. 307–324, 1999.
View at: Google Scholar
J. V. Guadagno, G. A. Donnan, R. Markus, J. H. Gillard, and J.-C. Baron, “Imaging the ischaemic penumbra,” Current Opinion in Neurology, vol. 17, no. 1, pp. 61–67, 2004.
View at: Publisher Site | Google Scholar
C. A. Mathis, B. J. Bacskai, S. T. Kajdasz et al., “A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain,” Bioorganic and Medicinal Chemistry Letters, vol. 12, no. 3, pp. 295–298, 2002.
View at: Publisher Site | Google Scholar
Y. Wang, C. A. Mathis, G.-F. Huang et al., “Effects of lipophilicity on the affinity and nonspecific binding of iodinated benzothiazole derivatives,” Journal of Molecular Neuroscience, vol. 20, no. 3, pp. 255–260, 2003.
View at: Publisher Site | Google Scholar
W. E. Klunk, Y. Wang, G.-F. Huang, M. L. Debnath, D. P. Holt, and C. A. Mathis, “Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain,” Life Sciences, vol. 69, no. 13, pp. 1471–1484, 2001.
View at: Publisher Site | Google Scholar
J. R. Ballinger, “Imaging hypoxia in tumors,” Seminars in Nuclear Medicine, vol. 31, no. 4, pp. 321–329, 2001.
View at: Publisher Site | Google Scholar
R. J. Hodgkiss, “Use of 2-nitroimidazoles as bioreductive markers for tumour hypoxia,” Anti-Cancer Drug Design, vol. 13, no. 6, pp. 687–702, 1998.
View at: Google Scholar
S. S. Foo, D. F. Abbott, N. Lawrentschuk, and A. M. Scott, “Functional imaging of intratumoral hypoxia,” Molecular Imaging and Biology, vol. 6, no. 5, pp. 291–305, 2004.
View at: Publisher Site | Google Scholar
J. M. Hoffman, J. S. Rasey, A. M. Spence, D. W. Shaw, and K. A. Krohn, “Binding of the hypoxia tracer [ ${}^{3}H$ ]misonidazole in cerebral ischemia,” Stroke, vol. 18, no. 1, pp. 168–176, 1987.
View at: Google Scholar
R. Markus, D. C. Reutens, S. Kazui et al., “Topography and temporal evolution of hypoxic viable tissue identified by 18F-fluoromisonidazole positron emission tomography in humans after ischemic stroke,” Stroke, vol. 34, no. 11, pp. 2646–2652, 2003.
View at: Publisher Site | Google Scholar
Z. Li, T. Chu, X. Liu, and X. Wang, “Synthesis and in vitro and in vivo evaluation of three radioiodinated nitroimidazole analogues as tumor hypoxia markers,” Nuclear Medicine and Biology, vol. 32, no. 3, pp. 225–231, 2005.
View at: Publisher Site | Google Scholar
S. Levine and H. Payan, “Effects of ischemia and other procedures on the brain and retina of the gerbil (Meriones unguiculatus),” Experimental Neurology, vol. 16, no. 3, pp. 255–262, 1966.
View at: Publisher Site | Google Scholar
K. Ohno, U. Ito, and Y. Inaba, “Regional cerebral blood flow and stroke index after left carotid artery ligation in the conscious gerbil,” Brain Research, vol. 297, no. 1, pp. 151–157, 1984.
View at: Publisher Site | Google Scholar
D. I. Edwards, “Nitroimidazole drugs-action and resistance mechanisms—I: mechanisms of action,” Journal of Antimicrobial Chemotherapy, vol. 31, no. 1, pp. 9–20, 1993.
View at: Publisher Site | Google Scholar
D. I. Edwards, “Nitroimidazole drugs-action and resistance mechanisms—II: mechanisms of resistance,” Journal of Antimicrobial Chemotherapy, vol. 31, no. 2, pp. 201–210, 1993.
View at: Publisher Site | Google Scholar
S. J. Read, T. Hirano, D. F. Abbott et al., “The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography after ischemic stroke,” Annals of Neurology, vol. 48, no. 2, pp. 228–235, 2000.
View at: Publisher Site | Google Scholar
S. Levine and D. Sohn, “Cerebral ischemia in infant and adult gerbils. Relation to incomplete circle of Willis,” Archives of Pathology, vol. 87, no. 3, pp. 315–317, 1969.
View at: Google Scholar
D. E. Levy and J. B. Brierley, “Communications between vertebro-basilar and carotid arterial circulations in the gerbil,” Experimental Neurology, vol. 45, no. 3, pp. 503–508, 1974.
View at: Publisher Site | Google Scholar
K. Kahn, “The natural course of experimental cerebral infarction in the gerbil,” Neurology, vol. 22, no. 5, pp. 510–515, 1972.
View at: Google Scholar
T. Kirino, “Delayed neuronal death in the gerbil hippocampus following ischemia,” Brain Research, vol. 239, no. 1, pp. 57–69, 1982.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2007 Taiwei Chu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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