Life Sci. 2003 Aug 8;73(12):1577-85

Radiolabeling and biodistribution of methyl 2-(methoxycarbonyl)-2-(methylamino) bicyclo[2.1.1] -hexane -5-carboxylate, a potential neuroprotective drug

Yu M, Någren K, Chen YI, Livni E, Elmaleh D, Kozikowski A, Wang X, Jokivarsi K, Brownell AL.

Abstract

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.

PMID: 12865097