Evaluation of phosphoinositide turnover on ischemic human brain with 1-[1-C-11]-butyryl-2-palmitoyl-rac-glycerol using PET

It is important to evaluate cerebral function from neural signal transducti on in ischemic brain in judging morbid state and prognosis. We synthesized 1-[1-C-11]-butyryl-2-palmitoyl-rac-glycerol (DAG) for the purpose of imagin g the second messenger on PET and applied it to clinical cases of cerebral infarction. Methods: Five patients, who had ischemic stroke, were examined with PET. [O-15]-CO2 and [O-15]-O-2 inhalation methods were applied to cere bral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabo lic rate of oxygen (CMRO2). For the measurement of phosphoinositide turnove r after intravenous injection of DAG, dynamic PET data were collected conti nuously for 46 min. Arterial blood samples were taken to evaluate changes i n the serum concentration of DAG. To quantify the metabolic activity of ino sitol phospholipid, the incorporation constant k*(DAG) was calculated on th e basis of the kinetics of DAG. Results: The plasma concentration of DAG in creased rapidly and peaked 30 s after injection of DAG solution. In the nor mal cortex, DAG concentration increased gradually and reached a plateau bet ween 15 and 20 min after injection. In the ischemic core (infarction), DAG concentration increased slowly, and its peak concentration was lower than t hat in normal tissue. In comparison with blood flow and metabolic parameter s, k*(DAG) showed the best correlation with CMRO2, suggesting a reflection of neuronal activity. Locally, CBF and CMRO2 gradually decreased from the n ormal area toward the ischemic center (infarction), whereas k*(DAG) and OEF significantly decreased only in the ischemic center. Conclusion: The k*(DA G) of ischemic brain, including that caused by infarction, significantly co rrelated with CMRO2, suggesting that metabolic activity of inositol phospho lipid reflects neural viability. Maintained metabolic activity of inositol phospholipid in the region around the ischemic core indicated preservation of the signal transduction system through the metabotropic receptor.