Intraperitoneal Injection Improves the Uptake of Nanoparticle-Labeled High-Density Lipoprotein to Atherosclerotic Plaques Compared With Intravenous Injection: A Multimodal Imaging Study in ApoE Knockout Mice

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Intraperitoneal Injection Improves the Uptake of Nanoparticle-Labeled High-Density Lipoprotein to Atherosclerotic Plaques Compared With Intravenous Injection: A Multimodal Imaging Study in ApoE Knockout Mice. / Jung, Caroline; Kaul, Michael G; Bruns, Oliver T; Dučić, Tanja; Freund, Barbara; Heine, Markus; Reimer, Rudolph; Meents, Alke; Salmen, Sunhild C; Weller, Horst; Nielsen, Peter; Adam, Gerhard; Heeren, Jörg; Ittrich, Harald.

in: CIRC-CARDIOVASC IMAG, Jahrgang 7, Nr. 2, 01.03.2014, S. 303-11.

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@article{0bdbd0223811482683fa8bb74dc0747b,
title = "Intraperitoneal Injection Improves the Uptake of Nanoparticle-Labeled High-Density Lipoprotein to Atherosclerotic Plaques Compared With Intravenous Injection: A Multimodal Imaging Study in ApoE Knockout Mice",
abstract = "Background- The aim of this study was to assess whether high-density lipoprotein (HDL) labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and quantum dots was able to detect atherosclerotic lesions in mice after intravenous and intraperitoneal injection by multimodal imaging. Methods and Results- Nanoparticle-labeled HDLs (NP-HDLs) were characterized in vitro by dynamic light scattering and size exclusion chromatography with subsequent cholesterol and fluorescence measurements. For biodistribution and blood clearance studies, NP-HDLSPIOs radiolabeled with (59)Fe (NP-HDL59Fe-SPIOs) were injected intravenously or intraperitoneally into ApoE knockout mice (n=6), and radioactivity was measured using a gamma counter. NP-HDL accumulation within atherosclerotic plaques in vivo and ex vivo was estimated by MRI at 7 Tesla, ex vivo confocal fluorescence microscopy, x-ray fluorescence microscopy, and histological analysis (n=3). Statistical analyses were performed using a 2-tailed Student t-test. In vitro characterization of NP-HDL confirmed properties similar to endogenous HDL. Blood concentration time curves showed a biexponential decrease for the intravenous injection, whereas a slow increase followed by a steady state was noted for intraperitoneal injection. Radioactivity measurements showed predominant accumulation in the liver and spleen after both application approaches. NP-HDL59Fe-SPIOs uptake into atherosclerotic plaques increased significantly after intraperitoneal compared with intravenous injection (P<0.01). In vivo MRI showed an increased uptake of NP-HDL into atherosclerotic lesions after intraperitoneal injection, which was confirmed by ex vivo MRI, x-ray fluorescence microscopy, confocal fluorescence microscopy, and histological analysis. Conclusions- In vivo MRI and ex vivo multimodal imaging of atherosclerotic plaque using NP-HDL is feasible, and intraperitoneal application improves the uptake within vessel wall lesions compared with intravenous injection.",
author = "Caroline Jung and Kaul, {Michael G} and Bruns, {Oliver T} and Tanja Du{\v c}i{\'c} and Barbara Freund and Markus Heine and Rudolph Reimer and Alke Meents and Salmen, {Sunhild C} and Horst Weller and Peter Nielsen and Gerhard Adam and J{\"o}rg Heeren and Harald Ittrich",
year = "2014",
month = mar,
day = "1",
doi = "10.1161/CIRCIMAGING.113.000607",
language = "English",
volume = "7",
pages = "303--11",
journal = "CIRC-CARDIOVASC IMAG",
issn = "1941-9651",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

RIS

TY - JOUR

T1 - Intraperitoneal Injection Improves the Uptake of Nanoparticle-Labeled High-Density Lipoprotein to Atherosclerotic Plaques Compared With Intravenous Injection: A Multimodal Imaging Study in ApoE Knockout Mice

AU - Jung, Caroline

AU - Kaul, Michael G

AU - Bruns, Oliver T

AU - Dučić, Tanja

AU - Freund, Barbara

AU - Heine, Markus

AU - Reimer, Rudolph

AU - Meents, Alke

AU - Salmen, Sunhild C

AU - Weller, Horst

AU - Nielsen, Peter

AU - Adam, Gerhard

AU - Heeren, Jörg

AU - Ittrich, Harald

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Background- The aim of this study was to assess whether high-density lipoprotein (HDL) labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and quantum dots was able to detect atherosclerotic lesions in mice after intravenous and intraperitoneal injection by multimodal imaging. Methods and Results- Nanoparticle-labeled HDLs (NP-HDLs) were characterized in vitro by dynamic light scattering and size exclusion chromatography with subsequent cholesterol and fluorescence measurements. For biodistribution and blood clearance studies, NP-HDLSPIOs radiolabeled with (59)Fe (NP-HDL59Fe-SPIOs) were injected intravenously or intraperitoneally into ApoE knockout mice (n=6), and radioactivity was measured using a gamma counter. NP-HDL accumulation within atherosclerotic plaques in vivo and ex vivo was estimated by MRI at 7 Tesla, ex vivo confocal fluorescence microscopy, x-ray fluorescence microscopy, and histological analysis (n=3). Statistical analyses were performed using a 2-tailed Student t-test. In vitro characterization of NP-HDL confirmed properties similar to endogenous HDL. Blood concentration time curves showed a biexponential decrease for the intravenous injection, whereas a slow increase followed by a steady state was noted for intraperitoneal injection. Radioactivity measurements showed predominant accumulation in the liver and spleen after both application approaches. NP-HDL59Fe-SPIOs uptake into atherosclerotic plaques increased significantly after intraperitoneal compared with intravenous injection (P<0.01). In vivo MRI showed an increased uptake of NP-HDL into atherosclerotic lesions after intraperitoneal injection, which was confirmed by ex vivo MRI, x-ray fluorescence microscopy, confocal fluorescence microscopy, and histological analysis. Conclusions- In vivo MRI and ex vivo multimodal imaging of atherosclerotic plaque using NP-HDL is feasible, and intraperitoneal application improves the uptake within vessel wall lesions compared with intravenous injection.

AB - Background- The aim of this study was to assess whether high-density lipoprotein (HDL) labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and quantum dots was able to detect atherosclerotic lesions in mice after intravenous and intraperitoneal injection by multimodal imaging. Methods and Results- Nanoparticle-labeled HDLs (NP-HDLs) were characterized in vitro by dynamic light scattering and size exclusion chromatography with subsequent cholesterol and fluorescence measurements. For biodistribution and blood clearance studies, NP-HDLSPIOs radiolabeled with (59)Fe (NP-HDL59Fe-SPIOs) were injected intravenously or intraperitoneally into ApoE knockout mice (n=6), and radioactivity was measured using a gamma counter. NP-HDL accumulation within atherosclerotic plaques in vivo and ex vivo was estimated by MRI at 7 Tesla, ex vivo confocal fluorescence microscopy, x-ray fluorescence microscopy, and histological analysis (n=3). Statistical analyses were performed using a 2-tailed Student t-test. In vitro characterization of NP-HDL confirmed properties similar to endogenous HDL. Blood concentration time curves showed a biexponential decrease for the intravenous injection, whereas a slow increase followed by a steady state was noted for intraperitoneal injection. Radioactivity measurements showed predominant accumulation in the liver and spleen after both application approaches. NP-HDL59Fe-SPIOs uptake into atherosclerotic plaques increased significantly after intraperitoneal compared with intravenous injection (P<0.01). In vivo MRI showed an increased uptake of NP-HDL into atherosclerotic lesions after intraperitoneal injection, which was confirmed by ex vivo MRI, x-ray fluorescence microscopy, confocal fluorescence microscopy, and histological analysis. Conclusions- In vivo MRI and ex vivo multimodal imaging of atherosclerotic plaque using NP-HDL is feasible, and intraperitoneal application improves the uptake within vessel wall lesions compared with intravenous injection.

U2 - 10.1161/CIRCIMAGING.113.000607

DO - 10.1161/CIRCIMAGING.113.000607

M3 - SCORING: Journal article

C2 - 24357264

VL - 7

SP - 303

EP - 311

JO - CIRC-CARDIOVASC IMAG

JF - CIRC-CARDIOVASC IMAG

SN - 1941-9651

IS - 2

ER -