{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:28:13Z","timestamp":1791300493657,"version":"4.1.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocytes and macrophages could serve as a biomarker of disease progression and therapeutic intervention.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To noninvasively assess plaque inflammation with dextran nanoparticle (DNP)-facilitated hybrid positron emission tomography\/magnetic resonance imaging (PET\/MRI).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Using clinically approved building blocks, we systematically developed 13-nm polymeric nanoparticles consisting of cross-linked short chain dextrans, which were modified with desferoxamine for zirconium-89 radiolabeling (\n              <jats:sup>89<\/jats:sup>\n              Zr-DNP) and a near-infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in monocytes and macrophages (76.7%) and lower signal originating from other leukocytes, such as neutrophils and lymphocytes (11.8% and 0.7%,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05 versus monocytes and macrophages). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET\/MRI revealed high uptake of\n              <jats:sup>89<\/jats:sup>\n              Zr-DNP in the aortic root of apolipoprotein E knock out (ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) mice (standard uptake value, ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice versus wild-type controls, 1.9\u00b10.28 versus 1.3\u00b10.03;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor C-C chemokine receptor type 2 with short-interfering RNA decreased\n              <jats:sup>89<\/jats:sup>\n              Zr-DNP plaque signal (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) and inflammatory gene expression (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Hybrid PET\/MRI with a 13-nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.111.300576","type":"journal-article","created":{"date-parts":[[2013,1,9]],"date-time":"2013-01-09T13:40:46Z","timestamp":1357738846000},"page":"755-761","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":138,"title":["Polymeric Nanoparticle PET\/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques"],"prefix":"10.1161","volume":"112","author":[{"given":"Maulik D.","family":"Majmudar","sequence":"first","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongsoo","family":"Yoo","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund J.","family":"Keliher","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J.","family":"Truelove","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brena","family":"Sena","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha","family":"Dutta","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Borodovsky","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo F.","family":"Di Carli","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Anderson","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip K.","family":"Swirski","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Weissleder","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Nahrendorf","sequence":"additional","affiliation":[{"name":"From the Center for Systems Biology, Massachusetts General Hospital, Boston, MA (M.D.M., J.Y., E.J.K., J.J.T., Y.I., B.S., P.D., F.K.S., R.W., M.N.); Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (M.D.M., P.L.); Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (J.Y.); Alnylam Pharmaceuticals, Cambridge, MA (A.B., K.F.); Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.110.221150"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06803"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circimaging.108.839092"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.741181"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1989"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052723"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc200405d"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.08.066"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circimaging.110.959478"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2011.08.019"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.03.044"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.08.003"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.140"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-011-9284-0"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.112.245415"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.09.017"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.01.008"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/29788"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80139-2"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175202"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.061986"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.111.300576","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:45:48Z","timestamp":1715571948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.111.300576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1161\/CIRCRESAHA.111.300576"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.111.300576","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3]]},"assertion":[{"value":"2012-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-01-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-01-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}