Summary: Autoradiograms obtained after middle cere bral artery occlusion (MCAO) in spontaneously hyperten sive rats show that the 99mTc complex of a 2-nitroimid azole-derivatized propylene amine oxime (BMS-181321) is selectively retained in acutely ischemic brain before disruption of the blood-brain barrier (BBB), but not in the ischemic infarct. BMS-181321 is therefore a marker of ischemic tissue at risk of infarction and its uptake, unlike that of x-ray and magnetic resonance contrast agents, does not require disruption of the BBB. In keeping with this conclusion, we have found that the single-pass cere bral extraction fraction of BMS-181321 is 0.67 at normal rat whole-brain blood flow. Sequential single-photon Delineation of viable ischemic tissue that is a tar get of various intervention strategies represents an important goal of nuclear medicine (Goldstein, 1990;Gropler and Bergman, 1991; Heiss et aI., 1992). One approach to this problem involves local Abbreviations used: BBB, blood-brain barrier; EB, Evans Blue; lAP, iodoantipyrine; MCAO, middle cerebral artery oc clusion; 2NI, 2-nitroimidazole; PnAO, propylene amine oxime; rCBF, regional CBF; ROD, relative optical density; Ro!, region of interest; SHR, spontaneously hypertensive rat; SPECT, sin gle-photon emission computed tomography. 755emission computed tomographic images obtained from cats after MCAO show that the initial distribution of BMS-181321 approximates regional CBF and that selec tive retention subsequently produces a positive image within the ischemic territory. BMS-181321 is the first Tc complex able to indicate not only ischemia, but also isch emic tissue at risk of infarction. Use of this novel Tc complex to monitor biochemical events during ischemia may contribute to the clinical management of acute stroke. Key Words: Hypoxia-Ischemia-Misonid azole-Neuronal viability-Single-photon emission com puted tomography.

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Thus, acute regional ischemia in these studies was visualized as an increase in retention of BMS-181321, suggesting its applicability in the imaging of clinical conditions of myocardial hypoperfusion.

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