A rapid semi-preparative synthesis of radioactive methionine sulfoximine, which retains full biological activity

It is assumed that the glucose ulilization by central nervous system is an accurate reflect of cerebral activity. With positron emission tomography us ing 2-fluoro, 2-deoxyglucose, it become possible to visualise brain areas t hat are activated by a variety of tasks. In neuropathologies such as Alzhei mer disease, Parkinson disease, and epilepsies, it was shown that the cereb ral metabolism of glucose was modified. However molecular and cellular mech anism of glucose metabolism variation is still unknown. To study these mech anisms, we take as an example the case of the epilepsies. We choose to use an experimental model of epilepsy which is the administration of methionine sulfoximine to rodent. In addition to be a convulsant, methionine sulfoxim ine modifies the brain carbohydrate metabolism. In order to look for the ta rget(s) of methionine sulfoximine, we try to synthesize the radioactive for m of the latter molecule. During the the process of this synthesis, a higly toxic product, methionine sulfoxide, is generated. Therefore the separatio n of methionine sulfoximine and methionine sulfoxide must be quite complete . We describe, in the present paper, an easy method for the radioactive syn thesis of methionine sulfoximine, its purification, its characterization wi th a good yield, and the possibility of getting large amounts of the produc t. Moreover we demonstrate that the biological activity of the synthesized labelled methionine sulfoximine is similar to that of the commercialy avail able MSO, which could allow an in vivo and in vitro studies.