Radiolabeling and biodistribution of methyl 2-(methoxycarbonyl)-2-(methylamino) bicyclo[2.1.1] -hexane -5-carboxylate, a potential neuroprotective drug.
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 degrees 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-carboxylate ([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.
Yu
Meixiang
M
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Bartlett Hall 511R, Boston, MA 02114, USA. ymeixiang@partners.org
Någren
Kjell
K
Chen
Y Iris
YI
Livni
Elijahu
E
Elmaleh
David
D
Kozikowski
Alan
A
Wang
Xukui
X
Jokivarsi
Kimmo
K
Brownell
Anna-Liisa
AL
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D007553:Isotope Labeling / Q000379:methods; D018696:Neuroprotective Agents / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D001643:Bridged Bicyclo Compounds; D002250:Carbon Radioisotopes; D018696:Neuroprotective Agents; C476512:methyl-2-(methoxycarbonyl)-2-(methylamino)bicyclo(2.1.1)hexane -5-carboxylate