In vivo evaluation of the nitroimidazole-based thioflavin-T derivatives as cerebral ischemia markers.
Timely imaging and accurate interpretation of cerebral ischemia are required to identify patients who might benefit from more aggressive therapy, and nuclear medicine offers a noninvasive method for demonstrating cerebral ischemia. Three nitroimidazole-based thioflavin-T derivatives, N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl) propanamide (4NPBTA), N-[4-(benzothiazol-2-yl)phenyl]-3-(4-nitroimidazole-1-yl)-N-methylpropanamide (4NPBTA-1), and N-[4-(benzothiazol-2-yl)phenyl]-3-(2-nitroimidazole-1-yl) propanamide (2NPBTA), were radioiodinated and evaluated as possible cerebral ischemia markers. In normal mice, these compounds showed good permeation of the intact blood-brain barrier (BBB), high initial brain uptake, and rapid washout. In gerbil stroke models that had been subjected to right common carotid artery ligation to produce cerebral ischemia, [(131)I]2NPBTA, uptake in the right cerebral hemisphere decreased more slowly than that of the left, and the right/left hemisphere uptake ratios increased with time. Also, the right/left hemisphere uptake ratios correlated positively with the severity of the stroke. The results showed that [(131)I]2NPBTA had a specific location in the cerebral ischemic tissue. This represented a first step in finding new drugs and might provide a possible cerebral ischemic marker.
Chu
Taiwei
T
Bejing National Laboratory for Molecular Sciences (BNLMS), Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Li
Zejun
Z
Liu
Xinqi
X
Wang
Xiangyun
X