C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase)
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 tomog...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2002-04-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1162/15353500200202109 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Martin G. Pomper |
| collection | DOAJ |
| description | 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 11 C–MeCys–C(O)–Glu or 11 C-( S )-2-[3-(( R )-1-carboxy-2-methylsulfanyl-ethyl)-ureido]-pentanedioic acid ( 11 C-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 11 C-MCG was assayed in mice, and quantitative PET was performed in a baboon. 11 C-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, 11 C-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 11 C-MCG occurred in the mouse or baboon. These results suggest that 11 C-MCG may be useful for imaging GCP II in the periphery. |
| format | Article |
| id | doaj-art-6eb7dd6e45cf4dfba1dfa3c1e4b208fd |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2002-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-6eb7dd6e45cf4dfba1dfa3c1e4b208fd2025-01-03T00:10:42ZengSAGE PublishingMolecular Imaging1536-01212002-04-01110.1162/1535350020020210910.1162_15353500200202109C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase)Martin G. Pomper0John L. Musachio1Jiazhong Zhang2Ursula Scheffel3Yun Zhou4John Hilton5Atul Maini6Robert F. Dannals7Dean F. Wong8Alan P. Kozikowski9Johns Hopkins University School of MedicineJohns Hopkins University School of MedicineGeorgetown University Medical CenterJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineGeorgetown University Medical CenterImaging 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 11 C–MeCys–C(O)–Glu or 11 C-( S )-2-[3-(( R )-1-carboxy-2-methylsulfanyl-ethyl)-ureido]-pentanedioic acid ( 11 C-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 11 C-MCG was assayed in mice, and quantitative PET was performed in a baboon. 11 C-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, 11 C-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 11 C-MCG occurred in the mouse or baboon. These results suggest that 11 C-MCG may be useful for imaging GCP II in the periphery.https://doi.org/10.1162/15353500200202109 |
| spellingShingle | 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 C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase) Molecular Imaging |
| title | C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase) |
| title_full | C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase) |
| title_fullStr | C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase) |
| title_full_unstemmed | C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase) |
| title_short | C-MCG: Synthesis, Uptake Selectivity, and Primate PET of a Probe for Glutamate Carboxypeptidase II (NAALADase) |
| title_sort | c mcg synthesis uptake selectivity and primate pet of a probe for glutamate carboxypeptidase ii naaladase |
| url | https://doi.org/10.1162/15353500200202109 |
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