Feature | January 30, 2015

New Plaque-Detecting Nanoparticle Imaging Agent Enters Clinical Trials

Agent lights up arterial plaque during PET scans, could help identify high-risk patients

Pamela Woodard, nanoparticle, Washington University, PET scan, plaque

Pamela Woodard, M.D., led a team that designed a new imaging agent that may light up dangerous plaque in arteries.

Diagram of nanoparticle. The nanoparticle is unique in how it is targeted, according to Yongjian Liu, Ph.D., assistant professor of radiology and co-investigator on the project. Previous research demonstrated that a receptor called NPR-C is present on the surface of cells that line blood vessels and is increased in atherosclerotic plaque. So the investigators added a small molecule to the nanoparticle that seeks out and binds to NPR-C, specifically targeting the particle to potentially dangerous plaque.

January 30, 2015 — The U.S. Food and Drug Administration (FDA) has approved for human evaluation a nanoparticle-based imaging agent jointly developed at Washington University School of Medicine in St. Louis and the University of California, Santa Barbara, in collaboration with Texas A&M University. The imaging agent may illuminate dangerous plaque in arteries, and doctors hope to use it to identify patients at high risk of stroke.

“This is the first receptor-targeted nanoparticle agent for cardiovascular imaging approved for investigational use in humans,” said principal investigator Pamela K. Woodard, M.D., professor of radiology and of biomedical engineering. “Starting with bench research, then developing and testing the agent and taking it through the FDA process into human patients has involved an extensive team of basic scientists, clinical researchers and clinicians.”

In patients with atherosclerosis, plaque accumulates on the inner walls of arteries that deliver blood to the body.

“Plaque is a complex structure made up of cholesterol, calcified deposits and other substances, all of which can cause inflammation,” said Woodard, also director of the Center for Clinical Imaging Research at the Mallinckrodt Institute of Radiology at Washington University. “Depending on the severity of the inflammation, these plaques can be stable or progress to a vulnerable phase in which they rupture, leading to stroke or heart attack.”

According to Woodard, many studies have indicated that most patients with plaque narrowing a carotid artery won’t go on to have a stroke.

“With current technology — such as ultrasound — we can’t tell whether the plaque is vulnerable or stable,” she said. “So we can’t distinguish the high-risk patients who need surgery from low-risk patients who can be treated with medication alone. We designed this nanoparticle agent to develop a test that can detect these vulnerable plaques and identify those patients at highest risk of stroke and in need of surgery to remove the plaque.”

This nanoparticle agent illuminates plaque in any of the body’s arteries and can be detected with a positron emission tomography (PET) scan. Researchers recently began testing the safety of the nanoparticle in healthy individuals. They next will focus on patients with atherosclerosis who already are scheduled to undergo surgery to remove plaque from their carotid arteries.

“In this way, we’ll be able to see whether the areas that light up in the image because of our nanoparticles are the same areas that contain vulnerable plaque, as assessed from the surgeries,” Woodard said. “Once we show success imaging the carotid arteries, we will evaluate the nanoparticle agent in other vessels such as the coronary arteries, which represent a greater challenge because of their smaller size and complex motion.”

The nanoparticle also carries copper atoms, making it visible with a standard PET scanner. Similar small amounts of copper-64 regularly are used in PET scans, a technique common in cancer detection and therapy and neurologic imaging.

In addition, components of the nanoparticle also are designed to self-assemble in the watery environment of blood.

“The success of this nanoparticle system relies on the controlled self-assembly of functional polymers in water, which is driven by the careful design of hydrophilic (water-attracting) and hydrophobic (water-repelling) segments into the polymers,” said Craig J. Hawker, Ph.D., professor and director of the California Nanosystems Institute at the University of California, Santa Barbara. 

Added Woodard: “We have been able to develop this highly receptor-specific imaging technology because of the generous support from the National Heart, Lung and Blood Institute, our diverse and dedicated team of investigators and our extensive facilities that allow us to make this nanoparticle imaging agent in a sterile environment, meeting the FDA requirements for use in people.” 

According to the university’s Office of Technology Management, Pamela K. Woodard, Geoffrey E. Woodard, Rafaella Rossin and the late Michael J. Welch are the inventors of the patented NPR-C imaging method.

For more information: www.medicine.wustl.edu

Related Content

ASNC and SNMMI Release Joint Document on Diagnosis, Treatment of Cardiac Sarcoidosis
News | Cardiac Imaging | August 18, 2017
August 18, 2017 — The American Society of Nuclear Cardiology (ASNC) has released a joint expert consensus document wi
Houston Methodist Hospital Enters Multi-Year Technology and Research Agreement With Siemens Healthineers
News | Imaging | August 17, 2017
Houston Methodist Hospital and Siemens Healthineers have entered into a multi-year agreement to bring cutting-edge...
Study Demonstrates First Human Application of Novel PET Tracer for Prostate Cancer

Transaxial 11Csarcosine hybrid PET/CT showed a (triangulated) adenocarcinoma in the transition zone of the anterior right prostate gland on PET (A), CT (B), and a separately obtained T2?weighted MR sequence (C) with resulting PET/MRI registration (D). Image courtesy of M. Piert et al., University of Michigan, Ann Arbor, Mich.

News | Radiopharmaceuticals and Tracers | August 16, 2017
In the featured translational article in the August issue of The Journal of Nuclear Medicine, researchers at the...
PET/CT Tracer Identifies Vulnerable Lesions in Non-Small Cell Lung Cancer Patients

Example of a patient with an upper left lung NSCLC: A: FDG; B: FDG PET/CT; C: Planning radiotherapy based on FDG (66Gy) with BTVm (GTV), CTV and PTV; D: PET FMISO E: FMISO PET/CT; F: boost based on the FMISO PET (76Gy) with BTVh (biological hypoxic target volume) and PTV boost. Credit: QuantIF – LITIS EA 4108 – FR CNRS 3638, Henri Becquerel Cancer Center, Rouen, France

News | PET-CT | July 14, 2017
July 14, 2017 — Fluorine-18 (18F)-fluoromisonidazole (FMISO) is a positron emission tomography (PET)...
Novel PET Tracer Detects Small Blood Clots

PET images (MIP 0-60 min) of three Cynomolgus monkeys. Strong signals are detected at the sites where inserted catheters had roughened surfaces. Almost no other background signal is visible. Only accumulation in the gallbladder becomes visible at the bottom of the image. Credit: Piramal Imaging GmbH, Berlin Germany.

News | PET Imaging | July 07, 2017
July 7, 2017 — Blood clots in veins a
Sponsored Content | Videos | Clinical Decision Support | June 29, 2017
Rami Doukky, M.D., system chair, Division of Cardiology, professor of medicine, Cook County Health and Hospitals Syst
Dual-Agent PET/MR With Time of Flight Detects More Cancer

Tc-99m MDP bone scan (left) is negative for osseous lesions. NaF/FDG PET/MRI (right and second slide) confirms absence of bone metastases, but shows liver metastases. Image courtesy of Stanford University.

News | PET-MRI | June 20, 2017
Simultaneous injections of the radiopharmaceuticals fluorine-18 fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (...
Combined Optical and Molecular Imaging Could Guide Breast-Conserving Surgery

WLE specimen from a patient with a grade 3, ER-/HER2-, no special type (NST) carcinoma. (A) Cerenkov image; (B) Grey-scale photographic image overlaid with Cerenkov signal. An increased signal from the tumor is visible (white arrows); mean radiance is 871 ± 131 photons/s/cm2/sr, mean TBR is 3.22. Both surgeons measured the posterior margin (outlined in blue) as 2 mm (small arrow); a cavity shaving would have been performed if the image had been available intraoperatively. The medial margin (outlined in green) measured >5 mm by both surgeons. Pathology ink prevented assessing the lateral margin; a phosphorescent signal is visible (open arrows). (C) Specimen radiography image. The absence of one surgical clip to mark the anterior margin, and the odd position of the superior margin clip (white arrow) prevented reliable margin assessment. (D) Combined histopathology image from two adjacent pathology slides on which the posterior margin (bottom of image) and part of the primary tumor are visible (open arrows). The distance from the posterior margin measured 3 mm microscopically (double arrow). The medial margin is > 5 mm (not present in image). Credit: A. D. Purushotham, M.D., King’s College London, UK

News | Nuclear Imaging | June 20, 2017
June 20, 2017 — Breast-conserving surgery (BCS) is the primary treatment for early-stage...
Overlay Init