TY - JOUR
T1 - Radiolabeling and biodistribution of methyl 2-(methoxycarbonyl)-2-(methylamino) bicyclo [2.1.1] - hexane -5-carboxylate, a potential neuroprotective drug
AU - Yu, Meixiang
AU - Någren, Kjell
AU - Chen, Y. Iris
AU - Livni, Elijahu
AU - Elmaleh, David
AU - Kozikowski, Alan
AU - Wang, Xukui
AU - Jokivarsi, Kimmo
AU - Brownell, Anna Liisa
N1 - Funding Information:
This work was supported by the DOD grant DAMD17-99-1-9555 to A-LB.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/8/8
Y1 - 2003/8/8
N2 - Methyl 2-(methoxycarbonyl) -2-(methylamino) bicyclo[2.1.1] -hexane -5-carboxylate (MMMHC) is developed as a potential neuroprotective drug. It was labeled with C-11 from the desmethyl precursor methyl 2-(methoxycarbonyl)-2-amino bicyclo[2.1.1]-hexane-5-carboxylate with [11C]methyl triflate in acetone solution at 60°C with labeling yield of 69% and with radiochemical purity of >99%. Positron Emission Tomography (PET) studies in a normal rat showed that Methyl 2-(methoxycarbonyl)-2-([11C]methylamino)bicyclo[2.1.1]-hexane-5- ca2rboxylate ([11C] MMMHC) accumulated mainly in the cortical brain areas after iv administration. Frontal cortex/cerebellum ratios in a rat brain were 8.0/6.0, 6.8/4.2, 6.3/4.3, 5.5/4.2 and 5.2/4.5 percent of the injected dose in 100 ml at 2 min, 5 min, 10 min, 20 min and 40 min respectively after i.v. injection. During 20-40 min, 2.9 ± 0.4% of the total activity stayed in the brain. These results showed that MMMHC could be labeled with C-11 with high yield, and it passed the brain-blood barrier and accumulated in several brain regions.
AB - Methyl 2-(methoxycarbonyl) -2-(methylamino) bicyclo[2.1.1] -hexane -5-carboxylate (MMMHC) is developed as a potential neuroprotective drug. It was labeled with C-11 from the desmethyl precursor methyl 2-(methoxycarbonyl)-2-amino bicyclo[2.1.1]-hexane-5-carboxylate with [11C]methyl triflate in acetone solution at 60°C with labeling yield of 69% and with radiochemical purity of >99%. Positron Emission Tomography (PET) studies in a normal rat showed that Methyl 2-(methoxycarbonyl)-2-([11C]methylamino)bicyclo[2.1.1]-hexane-5- ca2rboxylate ([11C] MMMHC) accumulated mainly in the cortical brain areas after iv administration. Frontal cortex/cerebellum ratios in a rat brain were 8.0/6.0, 6.8/4.2, 6.3/4.3, 5.5/4.2 and 5.2/4.5 percent of the injected dose in 100 ml at 2 min, 5 min, 10 min, 20 min and 40 min respectively after i.v. injection. During 20-40 min, 2.9 ± 0.4% of the total activity stayed in the brain. These results showed that MMMHC could be labeled with C-11 with high yield, and it passed the brain-blood barrier and accumulated in several brain regions.
KW - Carbon-11
KW - Metabotropic glutamate receptors
KW - Neuroprotection
KW - Positron emission tomography
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U2 - 10.1016/S0024-3205(03)00482-X
DO - 10.1016/S0024-3205(03)00482-X
M3 - Article
C2 - 12865097
AN - SCOPUS:0038153950
SN - 0024-3205
VL - 73
SP - 1577
EP - 1585
JO - Life sciences
JF - Life sciences
IS - 12
ER -