Assessment of Glutamine Synthetase Activity by [13N]Ammonia Uptake in Living Rat Brain

Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [N-13] Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [N-13] ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. L-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [N-13] Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the g-glutamyl transferase reaction. Autoradiograms showed a decrease of [N-13] ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [O-15]H2O. The reduction of [N-13] ammonia uptake was closely related to the results of GS activity assay. These results indicated that [N-13] ammonia may enable measurement of GS activity in the living brain. (C) 2014 Wiley Periodicals, Inc.