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AVM Discussion

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howardjoel howardjoel 20 years ago
Edwin Neuwelt

http://wcbs.dayport.com/viewer/viewerpage.php?Art_ID=11930&PreloadContract_DefID =1&Contract_DefID=2&tf=video_player.tpl&Category_ID=49

http://www.ohsu.edu/bbb/drneuwelt.html

Clinicals-http://www.ohsu.edu/bbb/clintrials.html
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howardjoel howardjoel 20 years ago
New at this have 1 more.

"Once we realized that iron oxide nanoparticles had unique pharmacology and a very long half-life in blood, we thought this might be a good imaging modality, not just to see where viruses went, but where inflammatory regions in the brain are," Neuwelt said.

Robert Quencer, M.D., chairman of the Department of Radiology at the University of Miami School of Medicine, and chief of radiological services at Jackson Memorial Hospital in Miami, is editor-in-chief of the American Journal of Neuroradiology, which published one of the first articles on the use of nanoparticles in imaging human brain tissue in 2002.

Quencer called Neuwelt's study "significant" because ferumoxtran-10 stays around longer than gadolinium, allowing doctors to view the affected tissue throughout the surgical process by intraoperative MR. And exploration of the mechanism by which it's accumulated in cells may provide more insight about tumors and other areas where reactive cells are found.

"There are a lot of possibilities," he said. "One area would be in spinal cord tumors. There's no reason to suspect the uptake would be different in the spine. And it could be very valuable in guiding a biopsy."

Neuwelt's collaborators included Nesbit; Peter Varallyay, M.D., instructor in diagnostic radiology; Attila Bago, M.D., former research instructor in neurology; Leslie Muldoon, Ph.D., assistant professor of cell and developmental biology, and neurology; and Randal Nixon, M.D., assistant professor of pathology.



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howardjoel howardjoel 20 years ago
Video next.

Because ferumoxtran-10 can stay in brain lesions for days - it can be administered to patients 24 hours before surgery - and can image other, non-cancerous lesions, it has some advantages over gadolinium, a metal used as an MR contrast agent for 20 years and which must be administered just before surgery. But Neuwelt doesn't believe iron oxide nanoparticles will necessarily replace gadolinium as an imaging tool.

"It will complement gadolinium, but not replace it," he said. "Gadolinium is the gold standard. But ferumoxtran-10 gives us additional information we can't get in some patients with gadolinium. Using both kinds of contrast agents, we can get better diagnostic information and that has the potential to improve the patient's outcome."

In the Neuropathology and Applied Neurobiology study, which followed seven patients with primary and metastatic malignant tumors, researchers used Combidex, a ferumoxtran-10 manufactured by Advanced Magnetics Inc. of Cambridge, Mass. Each iron oxide nanoparticle is the size of a small virus and is much smaller than a bacterium but much larger than an atom or standard gadolinium contrast molecule, Neuwelt said.

"It's an iron oxide crystal surrounded with a carbohydrate or 'sugar' coating," Neuwelt said. This coating, called dextran, gives the particle a longer plasma half-life, allowing it to slowly slip through the blood-brain barrier, or BBB, the tightly knit group of cells lining the walls of blood vessels in the brain. The BBB serves as a natural defense system by blocking the entry of foreign substances, including therapeutic agents.

"Anytime there's an injury, it induces inflammation," Neuwelt said. Ferumoxtran-10 is "taken up by inflammatory cells in the brain. You can see them in stroke and MS, you can see them in tumors. Gadolinium is basically the size of a large atom and does not enter cells, while this contrast agent is the size of a small virus and does enter cells."

In addition, ferumoxtran-10 can be detected with an iron stain in the tissue removed by biopsy or surgery, allowing physicians to see it in brain tissue samples under a microscope. "Unlike any other MR contrast agent, you can compare the images from an MR scan with the tissue taken out at surgery," Neuwelt said.

And it's relatively safe when diluted and administered as an infusion, although it can cause an allergic-type reaction when administered too quickly, he said.

Neuwelt says he first learned about iron oxide nanoparticles 11 years ago at a National Institutes of Health conference on new medical imaging techniques. "I heard this talk, and they were using it for liver and lymph nodes and I said to myself, 'Well, we ought to be able use it for the brain as well,'" he recalled.

Soon after, in April 1994, Neuwelt and colleagues published a study in the journal Neurosurgery showing that iron oxide nanoparticles could be delivered across the blood-brain barrier to the brain cells of rats and could be seen with MR.




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howardjoel howardjoel 20 years ago
Notice the name Neuwelt. Watch for in Video posted next.

Public release date: 26-May-2004
[ Print This Article / Close This Window ]

Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University

Nanoparticles illuminate brain tumors for days under MRI
OHSU study finds tiny crystals also help brain lesion tissue to be viewed under microscope
PORTLAND, Ore. - A research team from Oregon Health & Science University and the Portland Veterans Affairs Medical Center is demonstrating some of the world's first clinical applications for nanometer-size particles in the brain.
The OHSU scientists have shown that an iron oxide nanoparticle as small as a virus can outline not only brain tumors under magnetic resonance imaging, but also other lesions in the brain that may otherwise have gone unnoticed, according to a study published in the journal Neuropathology and Applied Neurobiology.

So named because of its billionth-of-a-meter proportions, the iron oxide nanoparticle, ferumoxtran-10, can be viewed as a contrast agent under MR for more than 24 hours, sometimes as long as five days, said the study's lead author, Edward Neuwelt, M.D., professor of neurology and neurological surgery, OHSU School of Medicine, and the Portland VA Medical Center.

In a parallel study by Neuwelt and colleagues, to be presented in June to the American Society of Neuroradiology, ferumoxtran-10 also was found to provide a "stable imaging marker" during surgery to remove brain tumors, and it remains in the brain long enough for post-operative MR, even after surgical manipulation.

The studies' findings have the potential to assist image-guided brain surgery and improve diagnosis of lesions caused by multiple sclerosis, stroke and other neurological disorders, in addition to residual tumors.

"This is one of the first biologically specific nanoparticles to be used in clinical trials," said Neuwelt, director of OHSU's Blood-Brain Barrier Program, which studies ways of outwitting the brain's natural defense to treat people with brain tumors. "This is the first time it's been applied to look at inflammatory lesions in the brain, not just tumors. They're very interesting particles and they're safe."

Study co-author Gary Nesbit, M.D., associate professor of diagnostic radiology and neurological surgery, and the Dotter Interventional Institute, OHSU, agreed the nanoparticles show potential for providing insight into a variety of brain pathologies.

"We're learning that disease in the brain is a complex system that has active involvement with cells and membranes, so there's a lot of interest in other areas as well," Nesbit said.

He said this early research on ferumoxtran-10 must be expanded to a larger group of patients to help scientists learn more about how the material reaches certain tumors and lesions, and why.

"This contrast agent provides a completely different way of looking at enhancement patterns on MRI," Nesbit added. There are distinct differences in how tumors enhance with contrast agents. "The way the contrast agent gets there is completely different. What we need to find out is what the specific pattern of enhancement with this contrast agent means."





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howardjoel howardjoel 20 years ago
Presentations at ISMRM Suggest Combidex(R) Useful in Detecting the Spread of Breast and Prostate Cancers to Lymph Nodes
CAMBRIDGE, Mass., and PRINCETON, N.J., July 15 /PRNewswire-FirstCall/ -- Advanced Magnetics, Inc. (Amex: AVM) and Cytogen Corporation (Nasdaq: CYTO) today announced data showing that magnetic resonance imaging (MRI) with Combidex(R) (ferumoxtran-10), an investigational iron oxide nanoparticle, aids in the non-invasive diagnosis of metastatic lymph nodes. The data presented at the International Society for Magnetic Resonance in Medicine (ISMRM) 11th Scientific Meeting held in Toronto, July 10-16, 2003 was from a study that included patients with breast and prostate cancer.

One presentation entitled "Detection of Minimal Nodal Disease in Patients with Breast Cancer," was made by Dr. Mukesh Harisinghani, Assistant Radiologist at Massachusetts General Hospital. Dr. Harisinghani concluded that Combidex-enhanced MRI is a useful tool for characterizing lymph nodes in patients with breast cancer. Dr. Harisinghani also noted that one of the patients analyzed in this presentation was determined to be free of metastatic disease based on sentinel node mapping and biopsy of the sentinel node but that another lymph node was determined to be metastatic based on Combidex-enhanced imaging. This second node was confirmed to be metastatic after removal at surgery.

A second presentation on data from prostate cancer patients was made by Dr. Ralph Weissleder, Director of the Center for Molecular Imaging Research at Massachusetts General Hospital. Dr. Weissleder concluded that Combidex is a useful MRI contrast agent for characterizing lymph nodes in patients with prostate cancer, and that Combidex-enhanced images alone may suffice for lymph node characterization.

"The data presented here show the potential role that Combidex-enhanced imaging could have in the diagnosis of lymph node metastases," stated Jerome Goldstein, Chairman and Chief Executive Officer of Advanced Magnetics. "The results coming from Dr. Harisinghani's group at Massachusetts General Hospital have consistently shown the advantages that Combidex could have in assisting physicians in staging cancer patients. We continue to be encouraged by these results."

"Both of the presentations made at ISMRM build on the data we have seen for Combidex in a number of cancers that spread to the lymph nodes," said Michael Becker, President and Chief Executive Officer of Cytogen Corporation, which has exclusive U.S. marketing rights to Combidex. "This growing body of scientific data supports our belief that Combidex could be an important new tool for physicians and their patients in staging a variety of cancers."

Combidex, the lead product in Advanced Magnetics' development pipeline, received an approvable letter, subject to certain conditions, from the U.S. Food and Drug Administration (FDA) for use in the diagnosis of metastatic lymph nodes. Advanced Magnetics continues to work with the FDA to resolve the outstanding issues from the approvable letter in an effort to bring Combidex to the market.


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howardjoel howardjoel 20 years ago
Imaging systems have never reliably shown tumors this small before anywhere in the body. Up to now, the smallest tumors detectable by MRI have been about one centimeter — the size of a fingernail.

Conventional MRI uses a magnetic field, which allows doctors to see enough only to gauge the size of lymph nodes. Nodes bigger than one centimeter are generally considered cancerous; however, they are not always cancerous, while some smaller nodes are. The new technique shows detail within the nodes that reveals cancer's presence.

The researchers gave patients an imaging agent known as lymphotropic superparamagnetic nanoparticles, which are specks of iron oxide less than a billionth of an inch across. Normally, the liver sucks up imaging agents before they reach the lymph nodes, but these particles are so small, they seep into the lymph system.

The technique appeared to work in cancerous lymph nodes from half to one centimeter, which would normally go unnoticed with regular MRI. It detected 96 percent of cancerous nodes that size, compared with a detection rate of 29 percent for regular MRI, and it found 41 percent of cancerous nodes smaller than half a centimeter, which are invisible to conventional MRI.

When spreading cancer has already reached the lymph nodes, doctors typically order radiation or hormonal treatments.

The researchers did not report any major side effects from the imaging agent.

"I would anticipate that it's going to get approved, and I would anticipate that it's going to be a big seller," said Dr. Otis Brawley, a cancer specialist at Emory University in Atlanta.


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howardjoel howardjoel 20 years ago

CBS news ran a feature story on "Iron Oxide Nanoparticles" for brain tumors on the evenings news. Did anyone catch it not sure if they mentioned the Dr. or Hospital as I was on the computer at the time. These are the dots that make me believe AVM is involved.

Notice Dr. Mukesh Harisinghani!!!

New MRI Detects Tiniest Of Tumors

BOSTON, June 18, 2003



(Photo: AP/CBS)



"Even if it only works this well for prostate cancer, it's a significant advance."
Dr. Jeffrey Brown, radiologist



(AP) An enhanced type of MRI can detect much smaller tumors than ever before — some tinier than a pea — in an advance that could open a new age in diagnosing cancer without surgery, researchers say.

The experimental technique examines the lymph nodes for signs of spreading cancer.

Doctors already routinely use magnetic resonance imaging, or MRI, to check the lymph nodes to see whether cancer that originated somewhere else in the body — say, in the breast or the prostate gland — is spreading. But the enhanced technique proved superior to conventional MRIs when tested with cancer that had spread from the prostate.

The leader of the research, Dr. Mukesh Harisinghani, said his team has also had preliminary success using the approach to detect the spread of breast, testicular, bladder and kidney cancer.

In the prostate study, the technique found 63 cancerous lymph nodes in 33 patients. Conventional MRI would have missed 71 percent of the nodes, and the spreading cancer would have gone undetected in nine patients.

"Even if it only works this well for prostate cancer, it's a significant advance," said Dr. Jeffrey Brown, a radiologist at Washington University in St. Louis.

Earlier detection of spreading prostate cancer would allow more aggressive treatment sooner, help doctors track the response, and spare some patients unnecessary removal of the prostate gland or lymph nodes. About 200,000 prostate cancer cases are diagnosed in the United States each year, and 32,000 people die from it.

The Food and Drug Administration is considering whether to approve the new technique. It is unclear when the FDA might decide.

Dr. Samuel Wickline, who studies imaging at Washington University, said this method and others like it will eventually "allow us to diagnose things that you can't even see with any imaging" now in use.

The study, funded partly by the National Cancer Institute, was carried out by Massachusetts General Hospital in Boston and University Medical Center in Nijmegen, the Netherlands. The findings appear in Thursday's New England Journal of Medicine.

The method relies on minuscule magnetic particles, known as nanoparticles, to enhance an MRI. Acting like a television's contrast dial, the injected particles collect in the immune system's lymph nodes and create a clearer separation between dark and light areas in the image.




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howardjoel howardjoel 20 years ago
Initiated at Jefferies -BUY Aug 20, 2004
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howardjoel howardjoel 20 years ago
"Combidex (ferumoxtran-10) is an investigational molecular imaging agent consisting of iron oxide nanoparticles for use in conjunction with magnetic resonance imaging (MRI) to aid in the differentiation of cancerous from non-cancerous lymph nodes. Lymph nodes are frequently the site for metastases of many different types of cancer, particularly breast cancer and prostate cancer. Computed tomography (CT) and MRI are the methods currently used for imaging lymph nodes. Current guidelines for imaging lymph nodes are that nodes greater than 10 mm in size are usually deemed cancerous while nodes less than 10 mm in size are generally presumed normal. CT and MRI cannot distinguish between lymph nodes that are enlarged due to the infiltration of cancerous cells as opposed to inflammation nor can these methods reliably detect disease in nodes that are not enlarged. Clinical studies have shown that Combidex accumulates in non-cancerous lymph node tissue which could enable doctors using MRI to have improved diagnostic confidence in differentiating between normal and diseased lymph nodes.

In the United States, an approvable letter was received from the U.S. Food and Drug Administration for Combidex in June 2000. In June 2004, we announced that a response to the approvable letter was submitted to the FDA and that the FDA requested that we provide certain additional details underlying the existing supporting data in the submission in order to make the submission a complete response to the approvable letter."



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