Woodard Group
Pamela K. Woodard, M.D.
Acute Vascular Injury
Division of Radiological Sciences
School of Medicine
Washington University in Saint Louis
510 South Kingshighway Blvd.
St. Louis, MO 63110
phone: (314) 362-9989
fax: (314) 362-3882
Goals for the Initial PEN grant
Within the NHLBI-PEN the Woodard Group will focus on Natriuretic peptide (NP) mediated imaging of atherosclerotic plaque. One target to be imaged with nanoparticles is the NP receptor. Natriuretic peptides (ANF, BNP and CNP) have potent anti proliferative and antimigratory effects on vascular smooth muscle cells. These properties make NPs relevant to the study of human atherosclerosis because vascular cell proliferation and migration are central to the pathophysiology of atherosclerosis. Preliminary studies have been performed in which two rats (one JCR:LA-cp rat with atherosclerotic disease, and one control) were injected with 64Cu-DOTA labeled CNP. Dynamic microPET images (5 sec/frame over the first 2 minutes and 15 sec/frame over minutes 2-5) showed tracer activity in the aorta on summed images obtained from 0-2 minutes, separate from blood pool activity in the diseased rat (see Figure below). No aortic radiotracer activity was identified in the control animal. Histopathology demonstrated no evidence of atherosclerosis in the control animal. The aorta of the diseased animal showed mild to moderate multi focal hemorrhage, hyperplastic media and accumulation of lipid-filled macrophages at the arch in the region of radiotracer activity. We will compare these directly labeled natriuretic peptides with nanoparticles where the nanoparticles have both the positron emitting nuclide and the unlabeled natiuretic peptides attached to the surface. Initially biodistribution and microPET imaging will be carried out. Nanoparticles will also be labeled with optical probes as well as gadolinium. The optical and MR images will then be compared with the microPET imaging.
This group will also facilitate the implementation of the small animal clinical field (3T) MR imaging for this and any other promising gadolinium-labeled nanoparticle and assist in the development of small animal models for atherosclerosis.
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| Image of rat with atherosclerotic aortic arch and with no disease |
Facilities
Dr. Woodard's group works within the Cardiovascular Imaging Laboratory (R. Gropler, Director). The Cardiovascular Imaging Laboratory (CVIL) is one of the laboratories within the Division of Radiological Sciences of the Mallinckrodt Institute of Radiology at Washington University Medical Center. The Cardiovascular Imaging Laboratory consists of 3000 square feet within the East Building (research building) of the Mallinckrodt Institute of Radiology. All MR research personnel and equipment are located in this building. The laboratory has office space for 27 people and includes a computer room. Current laboratory personnel include 6 faculty, 2 senior scientists, 1 computer scientist, 3 research associates, 3 research fellows, 5 research nurses/coordinators, 3 technical staff and a secretary. There are also 4 students. In addition, shared resources include two conference rooms, three lead and concrete-enforced rooms which house two 1.5 T MR scanners, and two examination rooms (for physical examinations, starting IV lines, etc.).
Many of the research techniques developed on the MRI equipment in the East Building Imaging Center have been transported to the clinical scanners and used in clinical research studies. These clinical systems have a configuration identical to the research scanner located in the East Building to enable easy transfer of research technology to the clinical setting.
People
Pamela K. Woodard, M.D.
Co-investigator
University Box 8131
Mallinckrodt Institute of Radiology
Washington University School of Medicine
510 S. Kingshighway Blvd.
St. Louis, MO 63110
Phone: (314) 362-9989
Fax: (314) 747-3882
woodardp@mir.wustl.edu
Jie Zheng, Ph.D.
Co-investigator
University Box 8131
Mallinckrodt Institute of Radiology
Washington University School of Medicine
510 S. Kingshighway Blvd.
St. Louis, MO 63110
Phone: (314) 747-4608
Fax: (314) 747-3882
zhengj@mir.wustl.edu