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.
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 FVBmice (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.
Authors: Patrick M Winter; Anne M Morawski; Shelton D Caruthers; Ralph W Fuhrhop; Huiying Zhang; Todd A Williams; John S Allen; Elizabeth K Lacy; J David Robertson; Gregory M Lanza; Samuel A Wickline Journal: Circulation Date: 2003-10-13 Impact factor: 29.690
Authors: Makan Khoshnejad; Vladimir V Shuvaev; Katherine W Pulsipher; Chuanyun Dai; Elizabeth D Hood; Evguenia Arguiri; Melpo Christofidou-Solomidou; Ivan J Dmochowski; Colin F Greineder; Vladimir R Muzykantov Journal: Bioconjug Chem Date: 2016-01-15 Impact factor: 4.774
Authors: Toshiro Kitagawa; Hisanori Kosuge; Edwin Chang; Michelle L James; Tomoaki Yamamoto; Bin Shen; Frederick T Chin; Sanjiv S Gambhir; Ronald L Dalman; Michael V McConnell Journal: Circ Cardiovasc Imaging Date: 2013-08-30 Impact factor: 7.792
Authors: Makan Khoshnejad; Colin F Greineder; Katherine W Pulsipher; Carlos H Villa; Burcin Altun; Daniel C Pan; Andrew Tsourkas; Ivan J Dmochowski; Vladimir R Muzykantov Journal: Bioconjug Chem Date: 2018-02-19 Impact factor: 4.774
Authors: Makan Khoshnejad; Hamideh Parhiz; Vladimir V Shuvaev; Ivan J Dmochowski; Vladimir R Muzykantov Journal: J Control Release Date: 2018-03-06 Impact factor: 9.776