title: Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of ¹⁸F-FDG PET Imaging in Ischemic Stroke Treatment.
abstract: Strategies to promote angiogenesis can benefit cerebral ischemia. We determined whether liposomal delivery of angiogenic peptides with a known biologic activity of vascular endothelial growth factor benefitted cerebral ischemia. Also, the study examined the potential of (18)F-FDG PET imaging in ischemic stroke treatment.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 40) underwent 40 min of middle cerebral artery occlusion. After 15 min of reperfusion, the rats (n = 10) received angiogenic peptides incorporated into liposomes. Animals receiving phosphate-buffered solution or liposomes without peptides served as controls. One week later, (18)F-FDG PET imaging was performed to examine regional changes in glucose utilization in response to the angiogenic therapy. The following day, (99m)Tc-hexamethylpropyleneamine oxime autoradiography was performed to determine changes in cerebral perfusion after angiogenic therapy. Corresponding changes in angiogenic markers, including von Willebrand factor and angiopoietin-1 and -2, were determined by immunostaining and polymerase chain reaction analysis, respectively.
  
  
  RESULTS
  A 40-min period of middle cerebral artery occlusion decreased blood perfusion in the ipsilateral ischemic cortex of the brain, compared with that in the contralateral cortex, as measured by (99m)Tc-hexamethylpropyleneamine oxime autoradiography. Liposomal delivery of angiogenic peptides to the ischemic hemisphere of the brain attenuated the cerebral perfusion defect compared with controls. Similarly, vascular density evidenced by von Willebrand factor-positive staining was increased in response to angiogenic therapy, compared with that of controls. This increase was accompanied by an early increase in angiopoietin-2 expression, a gene participating in angiogenesis. (18)F-FDG PET imaging measured at 7 d after treatment revealed that liposomal delivery of angiogenic peptides facilitated glucose utilization in the ipsilateral ischemic cortex of the brain, compared with that in the controls. Furthermore, the change in regional glucose utilization was correlated with the extent of improvement in cerebral perfusion (r = 0.742, P = 0.035).
  
  
  CONCLUSIONS
  Liposomal delivery of angiogenic peptides benefits cerebral ischemia. (18)F-FDG PET imaging holds promise as an indicator of the effectiveness of angiogenic therapy in cerebral ischemia.
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Hyosook
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea jayjeong@jbnu.ac.kr.
authors.forename: Hwan-Seok
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Phil-Sun
authors.initials: PS
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea jayjeong@jbnu.ac.kr.
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Na
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: JeongIl
authors.initials: J
authors.lastname: Kwon
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: SeokTae
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging & Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea jayjeong@jbnu.ac.kr.
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D002545:Brain Ischemia / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation; D016503:Drug Delivery Systems; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry; D007511:Ischemia / Q000000981:diagnostic imaging* / Q000628:therapy; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D064847:Multimodal Imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging; D010455:Peptides / Q000737:chemistry*; D010477:Perfusion; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000000981:diagnostic imaging* / Q000628:therapy; D013667:Technetium / Q000737:chemistry; D019690:Technetium Tc 99m Exametazime / Q000737:chemistry; D014057:Tomography, X-Ray Computed
chemical_list: D008081:Liposomes; D010455:Peptides; D019788:Fluorodeoxyglucose F18; D019690:Technetium Tc 99m Exametazime; D013667:Technetium; D005947:Glucose
keywords: 18F-FDG PET imaging; angiogenic peptides; liposomes; therapy