Imaging Cerebral Ischemia, Using a New [18F]-Labeled 2-Nitroimidazole Analog, [18F]FRP170

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(Introduction) 2-Nitroimidazole compounds are well-known radiosensitive sensitizers of hypoxic cells, and they have been applied to radiotherapy for malignant tumors. These compounds accumulate selectively in hypoxic cells. In the present study, we performed imaging of cerebral ischemia in animal experiments using a new hypoxic marker, ^<18>F-FRP170, which may enable depiction of the penumbra region that is still viable even under hypoxic conditions in cerebral ischemia and can be recovered by revascularization. (Materials and Methods) Male SD rats were used in this study. Rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Inserted nylon thread embolus into the left internal carotid artery resulted in blocking blood flow into the middle cerebral artery. 30 minutes after left middle cerebral artery occlusion, 74MBq of [18F]FRP170 was injected intravenously. At 210 minutes post-occlusion, 0.185MBq of [14C]IAP was injected as a blood flow marker. Anesthetize … More d rats were decapitated 10 seconds after the start of the [14C]IAP injection. The brains were removed rapidly from the skull and frozen in dry ice. 20□m thick coronal sections were cut on a cryostat microtome. The sections were placed in contact with general-use imaging plates. The autoradiographic images were obtained. 15 square regions of interest were placed on the [14C]IAP image throughout the ischemic hemisphere and nonischemic hemisphere. We put the ROIs on the other image at the same sites as the [18F]FRP170 image using the traced film. The uptake values in each ROI were expressed as the autoradiographic intensities. Profile curves of two radiopharmaceuticals were obtained and compared. (Results) The increased uptake areas of [18F]FRP170 were correspondent to slightly to moderately decreased perfusion areas, were also shown around decreased perfusion areas. We estimated those areas to be the regions of hypoxia or penumbra. Severely decreased perfusion areas with decreased uptake of [18F]FRP170 were shown. We estimated those areas to be the regions of ischemic core or infarction. (Conclusion) The method described here allowed us to differentiate between the ischemic center and the penumbra. Clinical application of this agent will provide useful information for determining whether reconstruction of the blood circulation or thrombolytic therapy should be applied. However, further studies are required before this agent can be used clinically. Less