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Molecular Imaging and Biology

, Volume 14, Issue 3, pp 315–324 | Cite as

RGD-Conjugated Human Ferritin Nanoparticles for Imaging Vascular Inflammation and Angiogenesis in Experimental Carotid and Aortic Disease

  • Toshiro Kitagawa
  • Hisanori Kosuge
  • Masaki Uchida
  • Monica M. Dua
  • Yasunori Iida
  • Ronald L. Dalman
  • Trevor Douglas
  • Michael V. McConnellEmail author
Research Article

Abstract

Purpose

Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg–Gly–Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease.

Procedures

Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n = 16). AAAs were induced by angiotensin II infusion in apoE−/− mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging.

Results

RGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88 ± 0.30 vs. 1.17 ± 0.10, p = 0.04; AAA: 2.59 ± 0.24 vs. 1.82 ± 0.16, p = 0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions.

Conclusions

RGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.

Key words

Vascular disease Nanoparticles Inflammation Angiogenesis Atherosclerosis Aneurysms RGD Ferritin 

Notes

Acknowledgments

We thank Dr. Matthew Bogyo and his laboratory for their assistance with mouse fluorescence molecular tomography. We thank support from the National Institutes of Health (R21 EB005364, R01 HL078678, P50 HL083800).

Disclosures

Dr. McConnell's laboratory receives research support from GE Healthcare and he is on a scientific advisory board for Kowa, Inc. Dr. Dalman's laboratory receives AAA research support from Medtronic AVE and Carolus Pharmaceuticals. The other authors have no potential conflicts of interest.

Supplementary material

11307_2011_495_MOESM7_ESM.jpg (57 kb)
Supplemental Figure 1 Bio-distribution analysis of RGD-HFn and HFn based on ex vivo Cy5.5 signal. The distribution of nanoparticles in the major organs after 48 hours was similar between RGD+ (injected with RGD-HFn-Cy5.5) and RGD (injected with HFn-Cy5.5) groups (p = NS RGD+ vs. RGD for all organs) (JPEG 57 kb)
11307_2011_495_MOESM8_ESM.jpg (43 kb)
Supplemental Figure 2 Macrophage immunofluorescence staining of representative non-ligated right carotid arteries in RGD group. Immunofluorescence double staining for HFn-Cy5.5 and macrophages (stained with Mac-3) demonstrated very little macrophage infiltration and minimal Cy5.5 signal in non-diseased right carotid arteries (JPEG 42 kb)
11307_2011_495_MOESM9_ESM.jpg (105 kb)
Supplemental Figure 3 . Smooth muscle cell (SMC) immunofluorescence staining of representative ligated left carotid arteries. RGD-HFn-Cy5.5 and HFn-Cy5.5 both showed limited colocalization to carotid SMCs (see text for quantitative colocalization analysis) (JPEG 105 kb)
11307_2011_495_MOESM10_ESM.jpg (89 kb)
Supplemental Figure 4 . Smooth muscle cell (SMC) immunofluorescence staining of representative abdominal aortic aneurysms (AAA). RGD-HFn-Cy5.5 and HFn-Cy5.5 both showed limited colocalization to AAA SMCs (see text for quantitative colocalization analysis) (JPEG 88 kb)

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Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2011

Authors and Affiliations

  • Toshiro Kitagawa
    • 1
  • Hisanori Kosuge
    • 1
  • Masaki Uchida
    • 2
  • Monica M. Dua
    • 3
  • Yasunori Iida
    • 3
  • Ronald L. Dalman
    • 3
  • Trevor Douglas
    • 2
  • Michael V. McConnell
    • 1
    Email author
  1. 1.Division of Cardiovascular MedicineStanford University School of MedicineStanfordUSA
  2. 2.Department of ChemistryMontana State UniversityBozemanUSA
  3. 3.Division of Vascular SurgeryStanford University School of MedicineStanfordUSA

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