IMAGING ISCHEMIC TISSUE AT RISK OF INFARCTION DURING STROKE

Autoradiograms obtained after middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats show that the Tc-99m complex of a 2 -nitroimidazole-derivatized propylene amine oxime (BMS-181321) is sele ctively retained in acutely ischemic brain before disruption of the bl ood-brain barrier (BBB), but not in the ischemic infarct. BMS-181321 i s therefore a marker of ischemic tissue at risk of infarction and its uptake, unlike that of x-ray and magnetic resonance contrast agents, d oes not require disruption of the BBB. In keeping with this conclusion , we have found that the single-pass cerebral extraction fraction of B MS-181321 is 0.67 at normal rat whole-brain blood flow. Sequential sin gle-photon emission computed tomographic images obtained from cats aft er MCAO show that the initial distribution of BMS-181321 approximates regional CBF and that selective retention subsequently produces a posi tive image within the ischemic territory. BMS-181321 is the first Tc c omplex able to indicate not only ischemia, but also ischemic tissue at risk of infarction. Use of this novel Tc complex to monitor biochemic al events during ischemia may contribute to the clinical management of acute stroke.