Abstract
Successful development of iodinated ligands for various neurotransmitter receptors prompted us to explore the feasability of having iodinated ligands to target amyloid plaques of Alzheimer’s disease. Several potential iodinated tracers based on various chemical backbone structures have been successfully prepared and evaluated toward this purpose. High binding affinities for Aβ aggregates were consistently observed for those ligands. However, the desirable in vivo properties were generally missing in the majority of those iodinated ligands. Only ligands with the promising in vitro and in vivo characteristics such as IMPY will likely warrant their success to be potential imaging agents mapping amyloid plaques in living human brain.
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References
Agdeppa E. D., Kepe V., Shoghi-Jadid K., Satyamurthy N., Small G. W., Petric A., et al. (2001) In vivo and in vitro labeling of plaques and tangles in the brain of an Alzheimer’s disease patient: a case study. J. Nucl. Med. 42, 65P (abstract).
Ginsberg S. D., Galvin J. E., Lee V. M., Rorke L. B., Dickson D. W., Wolfe J. H., et al. (1999) Accumulation of intracellular amyloid-beta peptide (A beta 1–40) in mucopolysaccharidosis brains. J. Neuropathol. Exp. Neurol. 58, 815–824.
Gordon M. N., Holcomb L. A., Jantzen P. T., DiCarlo G., Wilcock D., Boyett K. W., et al. (2002) Time course of the development of Alzheimer-like pathology in the doubly transgenic PS1+APP mouse. Exp. Neurol. 173, 183–195.
Hardy J. and Selkoe D. J. (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356.
Janus C., Chishti M. A., and Westaway D. (2000) Transgenic mouse models of Alzheimer’s disease. Biochem. Biophys. Acta 1502, 63–75.
Klunk W. E., Wang Y., Huang G. F., Debnath M. L., Holt D. P., Shao L., et al. (2003) The binding of 2-(4′-methyl-aminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J. Neurosci. 23, 2086–2092.
Kung H. F., Alavi A., Chang W., Kung M.-P., Keyes J. W., Jr., Velchik M. G., et al. (1990) In vivo SPECT imaging of CNSD2 dopamine receptors: initial studies with iodine-123-IBZM in humans. J. Nucl. Med. 31, 573–579.
Kung H. F., Frederick D., Kim H.- J., McElgin W., Kung M.-P., Mu M., et al. (1996a) In vivo SPECT imaging of 5-HT1A receptors with [123I]p-MPPI in nonhuman primates. Synapse 24, 273–281.
Kung H. F., Kim H.-J., Kung M.-P., Meegalla S. K., Plössl K., and Lee H.-K. (1996b) Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur. J. Nucl. Med. 23, 1527–1530.
Kung H. F., Lee C.- W., Zhuang Z. P., Kung M.-P., Hou C., and Plössl K. (2001) Novel stilbenes as probes for amyloid plaques. J. Am. Chem. Soc. 123, 12740–12741.
Kung M.- P., Essman W. D., Frederick D., Meegalla S., Goodman M., Mu M., et al. (1995) IPT: a novel iodinated ligand for the CNS dopamine transporter. Synapse 20, 316–324.
Kung M.- P., Hou C., Zhuang Z.- P., Zhang B., Skovronsky D. M., Gur T., et al. (2002) IMPY: An improved thioflavin-T derivative for in vivo labeling of β-amyloid plaques. Brain Res. 956, 202–210.
Kung M.- P., Skovronsky D., Hou C., Zhuang Z.- P., Gur T., Zhang B., et al. (2003) Detection of amyloid plaques by radioligands for Aβ40 and Aβ42: potential imaging agents in Alzheimer’ patients. J. Mol. Neurosci. 20, 15–23.
Lee C.- W., Kung M.- P., Hou C., and Kung H. F. (2003) Dimethylamino-fluorenes: ligands for detecting β-amyloid plaques in the brain. Nucl. Med. Biol. 30, 573–580.
Ono M., Kung M.- P., Hou C., and Kung H. F. (2002) Benzofuran derivatives as Aβ-aggregate-specificimaging agents for Alzheimer’s disease. Nucl. Med. Biol. 29, 633–642.
Ono M., Wilson A., Nobrega J., Westaway D., Verhoeff P., Zhuang Z.- P., et al. (2003) 11C-Labeled stilbene derivatives as Aβ-aggregate-specific PET imaging agents for Alzheimer’s disease. Nucl. Med. Biol., submitted.
Selkoe D. J. (2000) The origins of Alzheimer disease: A is for amyloid. JAMA 283, 1615–1617.
Zhuang Z.- P., Kung M.- P., Hou C., Plössel K., Skovronsky D., Gur T. L., et al. (2001a) IBOX(2-(4′-dimethyl-aminophenyl)-6-iodobenzoazole): a ligand for imaging amyloid plaques in the brain. Nucl. Med. Biol. 28, 887–894.
Zhuang Z.- P., Kung M. -P., Hou C., Skovronsky D., Gur T. L., Trojanowski J. Q., et al. (2001) Radioiodinated styrylbenzenes and thioflavins as probes for amyloid aggregates. J. Med. Chem. 44, 1905–1914.
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Kung, MP., Zhuang, ZP., Hou, C. et al. Development and evaluation of iodinated tracers targeting amyloid plaques for SPECT imaging. J Mol Neurosci 24, 49–53 (2004). https://doi.org/10.1385/JMN:24:1:049
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DOI: https://doi.org/10.1385/JMN:24:1:049