Radioiodinated diacylglycerol analogue: a potential imaging agent for single-photon emission tomographic investigations of cerebral ischaemia.
Phospholipid metabolism is closely related to membrane perturbation in cerebral ischaemia. We investigated in vivo topographical lipid metabolism using an iodine-123-labelled diacylglycerol analogue, (1-(15-(4-iodine-123-iodophenyl)-pentadecanoyl)-2-stearoyl-rac-gly cerol) (123I-labelled DAG), in a middle cerebral artery (MCA) occlusion model with the aim of positive imaging of ischaemic insult. Sprague-Dawley rats underwent coagulation of the MCA to induce permanent occlusion. MCA occlusion times prior to injection of 123I-labelled DAG ranged from 15 min to 14 days. Each rat was injected with 11-37 MBq of 123I-labelled DAG via a tail vein. After 30 min, in vivo autoradiographs were reconstructed. Scanning of the living rat brain in this MCA occlusion model was performed using a gamma camera with a pinhole collimator. Cerebral infarctions were recognized in the frontal cortex, the parietal cortex and the lateral portion of the caudate-putamen by 2,3,5-triphenyltetrazolium hydrochloride staining. In infarcted regions (region 1), 123I-labelled DAG incorporation showed a slight decrease up to 12 h; it then increased up to 6 days and decreased thereafter. In peri-infarcted regions (region 2), the incorporation showed almost no change up to 12 h, then increased up to 5-6 days and decreased thereafter. In other regions (region 3), the incorporation showed no change. Lipid analysis showed that 123I-labelled DAG was metabolized to 15-(4-iodine-123-iodophenyl)-pentadecanoic acid by DAG lipase and to 123I-labelled phosphatidylcholine. Scanning of the ischaemic region showed higher accumulation than on the non-lesioned side. We established a method to visualize ischaemic foci as positive images. The early changes in 123I-labelled DAG incorporation were closely related to DAG lipase, which degraded the accumulated intrinsic DAG, and increased 123I-labelled DAG incorporation in the chronic stage involves several aspects of neural destruction in the process of autolysis. It is concluded that the reported method could have a clinical future.
Ohmori
Y
Y
Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Imahori
Y
Y
Ueda
S
S
Fujii
R
R
Wakita
K
K
Inoue
M
M
Tazawa
S
S
D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging*; D004075:Diglycerides / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013668:Technetium Tc 99m Aggregated Albumin; D016284:Technetium Tc 99m Pentetate; D015899:Tomography, Emission-Computed, Single-Photon
C011439:1,2-diacylglycerol; D004075:Diglycerides; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D013668:Technetium Tc 99m Aggregated Albumin; C057162:technetium Tc 99m DTPA HSA; C025391:omega-(4-iodophenyl)pentadecanoic acid; D016284:Technetium Tc 99m Pentetate