Hailey Houson1, Alexander Mdzinarishvili1, Hariprasad Gali1, Evgeny Sidorov2, Vibhudutta Awasthi3,4. 1. Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave, Oklahoma City, OK, 73117, USA. 2. Department of Neurology, College of Medicine, The University of Oklahoma Health Sciences Center, 920 Stanton L. Young Blvd, Suite 2040, Oklahoma City, OK, 73104, USA. 3. Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, 1110 N. Stonewall Ave, Oklahoma City, OK, 73117, USA. vawasthi@ouhsc.edu. 4. Hexakit, Inc., 2401 Cheval Pointe Dr, Edmond, OK, 73034, USA. vawasthi@ouhsc.edu.
Abstract
PURPOSE: Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[18F]fluoro-D-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice. PROCEDURES: The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1 mice by occluding the middle cerebral artery for 1 h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with 99mTc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins. RESULTS: The kit-based synthesis was able to convert up to 2.2 GBq of FDG into FGA within 5 min. PET images showed 375 % more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55 % of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of stroke mice. CONCLUSIONS: Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity.
PURPOSE:Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting strokepatients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[18F]fluoro-D-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice. PROCEDURES: The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1mice by occluding the middle cerebral artery for 1 h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with 99mTc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins. RESULTS: The kit-based synthesis was able to convert up to 2.2 GBq of FDG into FGA within 5 min. PET images showed 375 % more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55 % of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of strokemice. CONCLUSIONS: Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity.
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Authors: William J Powers; Alejandro A Rabinstein; Teri Ackerson; Opeolu M Adeoye; Nicholas C Bambakidis; Kyra Becker; José Biller; Michael Brown; Bart M Demaerschalk; Brian Hoh; Edward C Jauch; Chelsea S Kidwell; Thabele M Leslie-Mazwi; Bruce Ovbiagele; Phillip A Scott; Kevin N Sheth; Andrew M Southerland; Deborah V Summers; David L Tirschwell Journal: Stroke Date: 2018-01-24 Impact factor: 7.914
Authors: S J Read; T Hirano; D F Abbott; J I Sachinidis; H J Tochon-Danguy; J G Chan; G F Egan; A M Scott; C F Bladin; W J McKay; G A Donnan Journal: Neurology Date: 1998-12 Impact factor: 9.910
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