Glutamate carboxypeptidase II levels in rodent brain using [ 125I]DCIT quantitative autoradiography

Tomás R. Guilarte, Jennifer L. McGlothan, Catherine A. Foss, Jia Zhou, Warren D. Heston, Alan P. Kozikowski, Martin G. Pomper

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The ability to visualize quantitatively glutamate carboxypeptidase II (GCPII) levels in vivo could advance our understanding of its function in health and disease. In the current study, we synthesized and evaluated a radiolabeled (iodine-125) analog of N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-iodo-l- tyrosine (DCIT), a potent antagonist of GCPII activity. We examined the regional distribution of [125I]DCIT binding in the rodent brain using quantitative autoradiography in order to confirm the validity of this radioligand as a marker of GCPII in the brain. The ultimate goal is to develop an imaging agent for assessing GCPII levels in the living brain. The specific binding of [125I]DCIT to rat brain followed a regional distribution consistent with previous studies describing regional brain GCPII gene expression and activity. We found a modest rostrocaudal gradient in which specific binding of [125I]DCIT to GCPII was lowest in cortical regions, with increasing levels of binding in midbrain structures and high levels of binding in hindbrain and brainstem. Autoradiography of [125I]DCIT in GCPII knockout and wild type mouse brain showed a gene-dose dependency confirming the selectivity of this radioligand for GCPII. We propose that [125I]DCIT is a selective radioligand that can be used to quantify brain GCPII levels in vitro using quantitative autoradiography.

Original languageEnglish (US)
Pages (from-to)141-144
Number of pages4
JournalNeuroscience Letters
Volume387
Issue number3
DOIs
StatePublished - Oct 28 2005
Externally publishedYes

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Keywords

  • Glutamate carboxypeptidase II (GCPII/NAALADase) levels
  • Quantitative autoradiography
  • Rodent brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Guilarte, T. R., McGlothan, J. L., Foss, C. A., Zhou, J., Heston, W. D., Kozikowski, A. P., & Pomper, M. G. (2005). Glutamate carboxypeptidase II levels in rodent brain using [ 125I]DCIT quantitative autoradiography. Neuroscience Letters, 387(3), 141-144. https://doi.org/10.1016/j.neulet.2005.06.015