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.

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.