PMID- 27390157 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20220316 IS - 1535-5667 (Electronic) IS - 0161-5505 (Print) IS - 0161-5505 (Linking) VI - 57 IP - 12 DP - 2016 Dec TI - PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model. PG - 2006-2011 AB - The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent (64)Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location. METHODS: New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0- to 60-min dynamic whole-body PET/MR examination was performed after injection of approximately 111 MBq of (64)Cu-ATSM. After 24 h, a 0- to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of (18)F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 alpha subunit [HIF-1alpha]). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test. RESULTS: Elevated uptake of (64)Cu-ATSM was found in the rabbits' IF compared with the SF. (64)Cu-ATSM imaging demonstrated IF-to-SF SUV(mean) ratios (+/-SD) of 1.75 +/- 0.21 and 2.30 +/- 0.26 at 4 and 8 wk after injury, respectively. (18)F-FDG imaging demonstrated IF-to-SF SUV(mean) ratios of 1.84 +/- 0.12 at 8 wk after injury. IF-to-BM SUV(mean) ratios were significantly higher (P < 0.001) than SF-to-BM SUV(mean) ratios both 4 and 8 wk after injury for (64)Cu-ATSM and 8 wk after injury for (18)F-FDG (P < 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1alpha. CONCLUSION: The results show that hypoxia is present in this rabbit model of atherosclerosis and suggest that (64)Cu-ATSM PET/MR is a potentially promising method for the detection of hypoxic and potentially vulnerable atherosclerotic plaque in human subjects. CI - (c) 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. FAU - Nie, Xingyu AU - Nie X AD - Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. AD - Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri. FAU - Laforest, Richard AU - Laforest R AD - Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. FAU - Elvington, Andrew AU - Elvington A AD - Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri. FAU - Randolph, Gwendalyn J AU - Randolph GJ AD - Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri. FAU - Zheng, Jie AU - Zheng J AD - Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. FAU - Voller, Tom AU - Voller T AD - Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. FAU - Abendschein, Dana R AU - Abendschein DR AD - Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri. AD - Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; and. FAU - Lapi, Suzanne E AU - Lapi SE AD - Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri. AD - Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri. AD - Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri. FAU - Woodard, Pamela K AU - Woodard PK AD - Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri woodardp@mir.wustl.edu. AD - Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri. AD - Diabetic Cardiovascular Disease Center, Washington University in St. Louis, St. Louis, Missouri. LA - eng GR - P30 DK020579/DK/NIDDK NIH HHS/United States GR - T32 HL007081/HL/NHLBI NIH HHS/United States GR - UL1 TR000448/TR/NCATS NIH HHS/United States PT - Journal Article DEP - 20160707 PL - United States TA - J Nucl Med JT - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JID - 0217410 RN - 0 (Coordination Complexes) RN - 0 (Organometallic Compounds) RN - 0 (Thiosemicarbazones) RN - 0 (copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)) SB - IM MH - Animals MH - Atherosclerosis/*diagnostic imaging/metabolism/*pathology MH - Biological Transport MH - Cell Hypoxia MH - Coordination Complexes MH - Disease Models, Animal MH - Macrophages/metabolism MH - *Magnetic Resonance Imaging MH - *Multimodal Imaging MH - *Organometallic Compounds/metabolism MH - *Positron-Emission Tomography MH - Rabbits MH - *Thiosemicarbazones/metabolism PMC - PMC5126698 OTO - NOTNLM OT - 64Cu-ATSM OT - PET/MR OT - hypoxic atherosclerosis OT - rabbit model EDAT- 2016/07/09 06:00 MHDA- 2017/05/16 06:00 PMCR- 2017/06/01 CRDT- 2016/07/09 06:00 PHST- 2016/01/20 00:00 [received] PHST- 2016/06/07 00:00 [accepted] PHST- 2016/07/09 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/07/09 06:00 [entrez] PHST- 2017/06/01 00:00 [pmc-release] AID - jnumed.116.172544 [pii] AID - 172544 [pii] AID - 10.2967/jnumed.116.172544 [doi] PST - ppublish SO - J Nucl Med. 2016 Dec;57(12):2006-2011. doi: 10.2967/jnumed.116.172544. Epub 2016 Jul 7.