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MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor
Michael J Lipinski1, Vardan Amirbekian, Juan C Frias
1Zena and Michael A. Wiener Cardiovascular Institute, Marie-Josée and Henry R. Kravis Cardiovascular Health Center, Imaging Science Laboratories, Department of Radiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Abstract:
The ability to specifically image macrophages may enable improved detection and characterization of atherosclerosis. In this study we evaluated the in vitro uptake of gadolinium (Gd)-containing immunomicelles (micelles linked to macrophage-specific antibody), micelles, and standard contrast agents by murine macrophages, and sought to determine whether immunomicelles and micelles improve ex vivo imaging of apolipoprotein E knockout (ApoE KO) murine atherosclerosis. Murine RAW 264.7 macrophages were incubated with Gd-DTPA, micelles, and immunomicelles. Cell pellets were prepared and imaged using a 1.5 T MR system with an inversion recovery spin-echo sequence to determine the in vitro T1 values. Ex vivo analysis of mouse aortas was performed using a 9.4T MR system with a high-spatial-resolution sequence (78x39x78 microm3). The T1 value was significantly decreased in cells treated with micelles compared to Gd-DTPA (P<0.0001), and in cells incubated at 4 degrees C with immunomicelles compared to micelles (P<0.05). Ex vivo MRI signal intensity (SI) was significantly increased by 81% and 20% in aortas incubated with immunomicelles and micelles, respectively. Confocal microscopy demonstrated in vitro and ex vivo uptake of fluorescent immunomicelles by macrophages. Immunomicelles and micelles improve in vitro and ex vivo MR detection of macrophages, and may prove useful in the detection of macrophage-rich plaques.
Insights
Immunomicelles and micelles enhance magnetic resonance imaging (MRI) detection of macrophages in vitro and ex vivo. These novel agents show promise for improved imaging and characterization of atherosclerosis.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Cardiovascular Research
Background:
- Macrophages play a critical role in atherosclerosis development.
- Targeted imaging of macrophages could improve atherosclerosis detection and characterization.
- Current imaging methods may lack specificity for macrophage-rich plaques.
Purpose of the Study:
- To evaluate the in vitro uptake of gadolinium (Gd)-containing immunomicelles and micelles by murine macrophages.
- To determine if immunomicelles and micelles improve ex vivo MRI of atherosclerosis in apolipoprotein E knockout (ApoE KO) mice.
- To assess the potential of immunomicelles and micelles for macrophage imaging.
Main Methods:
- In vitro incubation of RAW 264.7 macrophages with Gd-DTPA, micelles, and immunomicelles.
- In vitro MRI using a 1.5 T system to measure T1 values.
- Ex vivo MRI of ApoE KO mouse aortas using a 9.4T system with high-spatial-resolution imaging.
- Confocal microscopy to confirm uptake of fluorescent immunomicelles.
Main Results:
- Significant decrease in T1 values in cells treated with micelles compared to Gd-DTPA (P<0.0001).
- Significant decrease in T1 values in cells treated with immunomicelles at 4°C compared to micelles (P<0.05).
- Ex vivo MRI signal intensity increased by 81% with immunomicelles and 20% with micelles in mouse aortas.
- Confocal microscopy confirmed macrophage uptake of fluorescent immunomicelles both in vitro and ex vivo.
Conclusions:
- Immunomicelles and micelles effectively enhance in vitro and ex vivo MR detection of macrophages.
- These targeted agents show potential for improved detection and characterization of macrophage-rich atherosclerotic plaques.
- Further research may validate their clinical utility in cardiovascular imaging.
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