PMID- 23300273
OWN - NLM
STAT- MEDLINE
DCOM- 20130625
LR  - 20220408
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 112
IP  - 5
DP  - 2013 Mar 1
TI  - Polymeric nanoparticle PET/MR imaging allows macrophage detection in 
      atherosclerotic plaques.
PG  - 755-61
LID - 10.1161/CIRCRESAHA.111.300576 [doi]
AB  - RATIONALE: 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. 
      OBJECTIVE: To noninvasively assess plaque inflammation with dextran nanoparticle 
      (DNP)-facilitated hybrid positron emission tomography/magnetic resonance imaging 
      (PET/MRI). METHODS AND RESULTS: 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 ((89)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%, P<0.05 versus monocytes and macrophages). DNP 
      colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI 
      revealed high uptake of (89)Zr-DNP in the aortic root of apolipoprotein E knock 
      out (ApoE(-/-)) mice (standard uptake value, ApoE(-/-) mice versus wild-type 
      controls, 1.9+/-0.28 versus 1.3+/-0.03; P<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 (89)Zr-DNP plaque signal (P<0.05) and inflammatory gene expression 
      (P<0.05). CONCLUSIONS: 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.
FAU - Majmudar, Maulik D
AU  - Majmudar MD
AD  - Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St., 
      Boston, MA 02114, USA.
FAU - Yoo, Jeongsoo
AU  - Yoo J
FAU - Keliher, Edmund J
AU  - Keliher EJ
FAU - Truelove, Jessica J
AU  - Truelove JJ
FAU - Iwamoto, Yoshiko
AU  - Iwamoto Y
FAU - Sena, Brena
AU  - Sena B
FAU - Dutta, Partha
AU  - Dutta P
FAU - Borodovsky, Anna
AU  - Borodovsky A
FAU - Fitzgerald, Kevin
AU  - Fitzgerald K
FAU - Di Carli, Marcelo F
AU  - Di Carli MF
FAU - Libby, Peter
AU  - Libby P
FAU - Anderson, Daniel G
AU  - Anderson DG
FAU - Swirski, Filip K
AU  - Swirski FK
FAU - Weissleder, Ralph
AU  - Weissleder R
FAU - Nahrendorf, Matthias
AU  - Nahrendorf M
LA  - eng
GR  - T32 HL094301/HL/NHLBI NIH HHS/United States
GR  - HHSN268201000044C/HL/NHLBI NIH HHS/United States
GR  - R01-HL096576/HL/NHLBI NIH HHS/United States
GR  - R01 HL096576/HL/NHLBI NIH HHS/United States
GR  - T32-HL094301/HL/NHLBI NIH HHS/United States
GR  - R01 HL095612/HL/NHLBI NIH HHS/United States
GR  - R01 HL095629/HL/NHLBI NIH HHS/United States
GR  - R01-HL095629/HL/NHLBI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20130108
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Apolipoproteins E)
RN  - 0 (Dextrans)
RN  - 0 (Radioisotopes)
RN  - C6V6S92N3C (Zirconium)
SB  - IM
MH  - Animals
MH  - Aorta/diagnostic imaging/pathology
MH  - Apolipoproteins E/deficiency/genetics
MH  - Dextrans
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Feasibility Studies
MH  - Macrophages/*diagnostic imaging/*pathology
MH  - Magnetic Resonance Imaging/*methods
MH  - Mice
MH  - Mice, Knockout
MH  - *Nanoparticles
MH  - Plaque, Atherosclerotic/*diagnostic imaging/*pathology
MH  - Positron-Emission Tomography/*methods
MH  - Radioisotopes
MH  - Sensitivity and Specificity
MH  - Zirconium
PMC - PMC3586287
MID - NIHMS435077
EDAT- 2013/01/10 06:00
MHDA- 2013/06/26 06:00
PMCR- 2013/03/02
CRDT- 2013/01/10 06:00
PHST- 2013/01/10 06:00 [entrez]
PHST- 2013/01/10 06:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
PHST- 2013/03/02 00:00 [pmc-release]
AID - CIRCRESAHA.111.300576 [pii]
AID - 10.1161/CIRCRESAHA.111.300576 [doi]
PST - ppublish
SO  - Circ Res. 2013 Mar 1;112(5):755-61. doi: 10.1161/CIRCRESAHA.111.300576. Epub 2013 
      Jan 8.