title: Imaging ischemic tissue at risk of infarction during stroke.
abstract: Autoradiograms obtained after middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats show that the 99mTc complex of a 2-nitroimidazole-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 cerebral extraction fraction of BMS-181321 is 0.67 at normal rat whole-brain blood flow. Sequential single-photon emission computed tomographic images obtained from cats after MCAO show that the initial distribution of BMS-181321 approximates regional CBF and that selective 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 ischemic 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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
authors.forename: R J
authors.initials: RJ
authors.lastname: Di Rocco
authors.forename: B L
authors.initials: BL
authors.lastname: Kuczynski
authors.forename: J P
authors.initials: JP
authors.lastname: Pirro
authors.forename: A
authors.initials: A
authors.lastname: Bauer
authors.forename: K E
authors.initials: KE
authors.lastname: Linder
authors.forename: K
authors.initials: K
authors.lastname: Ramalingam
authors.forename: J E
authors.initials: JE
authors.lastname: Cyr
authors.forename: Y W
authors.initials: YW
authors.lastname: Chan
authors.forename: N
authors.initials: N
authors.lastname: Raju
authors.forename: R K
authors.initials: RK
authors.lastname: Narra
mesh_terms: D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000175:diagnosis* / Q000378:metabolism; D002544:Cerebral Infarction / Q000209:etiology* / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000378:metabolism; D008297:Male; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D051381:Rats; D011918:Rats, Inbred SHR; D012307:Risk Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; C082027:BMS 181321