doi: 10.1161/CIRCIMAGING.108.788299
Original Articles |
Development of Receptor for Advanced Glycation End Products–Directed Imaging of Atherosclerotic Plaque in a Murine Model of Spontaneous Atherosclerosis
From the Division of Cardiology (Y.T., M.S., A.J.E., L.L.J.), Department of Medicine and Division of Surgical Science (Q.L., R.R., B.I.H., A.M.S.), Department of Surgery, Columbia University Medical Center, New York, NY; and Thomas Jefferson National Accelerator Facility (S.M.), Newport News, Va.
Correspondence to Yared Tekabe, PhD, Division of Cardiology, Department of Medicine, Columbia University Medical Center, 620 West 168 Street, New York, NY 10032. E-mail yt2166{at}columbia.edu
Received May 22, 2008; accepted September 23, 2008.
Background— The receptor for advanced glycation end products (RAGE) is implicated in the development and progression of atherosclerosis. We tested the hypothesis that 99mTc-labeled anti-RAGE F(ab')2 can be used as a noninvasive tool to image atherosclerotic lesions in apolipoprotein E–deficient (apoE–/–) mice.
Methods and Results— A sequence in the V-type Ig extracellular domain of RAGE was used to develop a peptide injected into rabbits; serum was retrieved, IgG prepared and affinity-purified, and pepsin-digested into F(ab')2. Thirteen 6-week apoE–/– mice were fed a Western diet. At 20 weeks, 6 were injected with 15.2±1.9 MBq (350 to 411 µCi) 99mTc-labeled anti-RAGE F(ab')2, 6 were injected with 99mTc-labeled control nonspecific IgG F(ab')2, and 1 was injected with dual-labeled 99mTc and rhodamine anti-RAGE F(ab')2. Four 20-week C57BL/6 mice were injected with 99mTc-labeled anti-RAGE F(ab')2. All mice were imaged on a high resolution mini-
camera 4 hours after injection and euthanized. The aortic tree was dissected and photographed, and the proximal aorta was sectioned for staining after scintillation counting. All 6 apoE–/– mice injected with 99mTc-labeled anti-RAGE F(ab')2 fragments showed focal tracer uptake in the proximal aorta (mean %ID/g, 1.98%). Disease and antibody controls showed no focal tracer uptake in the thorax (%ID/g, <1.0%). Histological sections of the proximal aorta showed American Heart Association class III lesions with lipid laden macrophages, smooth muscle cells, and positive staining for RAGE. On immunofluorescence, RAGE colocalized with macrophages.
Conclusion— These data show the feasibility of noninvasively imaging RAGE in atherosclerotic lesions in a murine model and confirm levels of RAGE expression sufficient to allow detection on in vivo imaging.
Key Words: atherosclerosis • imaging • RAGE
CLINICAL PERSPECTIVE
Related Articles
- "Feeling the RAGE" in the Atherosclerotic Vessel Wall
- Zahi A. Fayad and Esad Vucic
Circ Cardiovasc Imaging 2008 1: 178-179.[Extract] [Full Text] [PDF]
- Development of Receptor for Advanced Glycation End Products–Directed Imaging of Atherosclerotic Plaque in a Murine Model of Spontaneous Atherosclerosis
- Yared Tekabe, Qing Li, Rosa Rosario, Marija Sedlar, Stan Majewski, Barry I. Hudson, Andrew J. Einstein, Ann Marie Schmidt, and Lynne L. Johnson
Circ Cardiovasc Imaging 2008 1: 212-219.[Abstract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  Y. Tekabe, J. Luma, A. J. Einstein, M. Sedlar, Q. Li, A. M. Schmidt, and L. L. Johnson A Novel Monoclonal Antibody for RAGE-Directed Imaging Identifies Accelerated Atherosclerosis in Diabetes J. Nucl. Med., January 1, 2010; 51(1): 92 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. A. Fayad and E. Vucic "Feeling the RAGE" in the Atherosclerotic Vessel Wall Circ Cardiovasc Imaging, November 1, 2008; 1(3): 178 - 179. [Full Text] [PDF]
|
|