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 language | English (US) |
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Pages (from-to) | 96-101 |
Number of pages | 6 |
Journal | Molecular Imaging |
Volume | 1 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2002 |
Externally published | Yes |
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