11C-MCG: Synthesis, uptake selectivity, and primate PET of a probe for glutamate carboxypeptidase II (NAALADase)

Martin G. Pomper, John L. Musachio, Jiazhong Zhang, Ursula Scheffel, Yun Zhou, John Hilton, Atul Maini, Robert F. Dannals, Dean F. Wong, Alan P. Kozikowski

Research output: Contribution to journalArticle

Abstract

Imaging of glutamate carboxypeptidase II (GCP II), also known as N-acetylated α-linked L-amino dipeptidase (NAALADase), may enable study of glutamatergic transmission, prostate cancer, and tumor neovasculature in vivo. Our goal was to develop a probe for GCP II for use with positron emission tomography (PET). Radiosynthesis of 11C-MeCys-C(O)-Glu or 11C-(S)-2-[3-((R)-1-carboxy-2-methylsulfanyl-ethyl)-ureido] -pentanedioic acid (11C-MCG), an asymmetric urea and potent (K i = 1.9 nM) inhibitor of GCP II, was performed by C-11 methylation of the free thiol. Biodistribution of 11C-MCG was assayed in mice, and quantitative PET was performed in a baboon. 11C-MCG was obtained in 16% radiochemical yield at the end of synthesis with specific radioactivities over 167 GBq/mmol (4000 Ci/mmol) within 30 min after the end of bombardment. At 30 min postinjection, 11C-MCG showed 33.0 ± 5.1%, 0.4 ± 0.1%, and 1.1 ± 0.2% ID/g in mouse kidney (target tissue), muscle, and blood, respectively. Little radioactivity gained access to the brain. Blockade with unlabeled MCG or 2-(phosphonomethyl)pentanedioic acid (PMPA), another potent inhibitor of GCP II, provided sevenfold and threefold reductions, respectively, in binding to target tissue. For PET, distribution volumes (DVs) were 1.38 then 0.87 pre- and postblocker (PMPA). Little metabolism of 11C-MCG occurred in the mouse or baboon. These results suggest that 11C-MCG may be useful for imaging GCP II in the periphery.

Original languageEnglish (US)
Pages (from-to)96-101
Number of pages6
JournalMolecular imaging
Volume1
Issue number2
DOIs
StatePublished - Apr 1 2002

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Keywords

  • C-MCG
  • Glutamate carboxypeptidase
  • NAALADase
  • PET
  • Urea-based inhibitor

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

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