MEDICAL: RESEARCH: Imaging Technique Allows Researchers to Monitor Protein Changes in Mouse Tumors

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MEDICAL: RESEARCH: Imaging Technique Allows Researchers to Monitor Protein Changes in Mouse Tumors

David P. Dillard
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MEDICAL: RESEARCH:
Imaging Technique Allows Researchers to Monitor
Protein Changes in Mouse Tumors



Date: Wed, 1 Jul 2009 12:08:24 -0400
From: "NIH OLIB (NIH/OD)" <[hidden email]>
To: [hidden email]
Subject:  Imaging Technique Allows Researchers to Monitor
Protein Changes in Mouse Tumors



U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News



National Cancer Institute (NCI)
<http://www.nci.nih.gov/>


National Institute of Biomedical Imaging and Bioengineering (NIBIB)
<http://www.nibib.nih.gov/>



Embargoed for Release: Wednesday, July 1, 2009, 12:00 p.m., EDT



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Cheryl Fee NIBIB

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IMAGING TECHNIQUE ALLOWS RESEARCHERS TO MONITOR PROTEIN CHANGES IN MOUSE TUMORS



A new imaging technique can monitor, in living mice, the HER2 protein
found in above-normal amounts in many cases of breast cancer as well as
some ovarian, prostate and lung cancers. This new approach, once validated
in mice and pending further experiments, could provide a real-time
noninvasive method for identifying tumors in humans who express HER2 and
who would be candidates for targeted therapy directed against this
protein. It may also provide real-time information that will help
clinicians optimize treatment for individual patients. The study,
published in the July 2009 issue of The Journal of Nuclear Medicine, was
conducted by researchers at the National Cancer Institute (NCI) and the
National Institute of Biomedical Imaging and Bioengineering, both parts of
the National Institutes of Health.

The HER2 protein is overexpressed (produced at higher-than-normal levels)
in approximately 20 percent to 25 percent of breast cancers. Tumors that
overexpress HER2 are more aggressive and more likely to recur than tumors
that do not overexpress the protein. Targeted therapies directed against
HER2 can slow or stop the growth of tumors that overexpress it.

Currently, HER2 expression is measured in biopsy specimens - that is, in
tumor samples that have been removed from the body. However, expression of
HER2 in these samples may not accurately represent HER2 expression in the
tumor as a whole. Moreover, follow-up biopsies are not routinely performed
after the initial diagnosis, and there are no means to evaluate how long a
targeted therapy takes to reach its target, how effective it is, and how
long its effects last.

In this study, the research team used an imaging compound that consists of
a radioactive atom (fluorine-18) attached to an Affibody molecule, a small
protein that binds strongly and specifically to HER2. Affibody molecules,
developed by Affibody AB, Bromma, Sweden, are much smaller than antibodies
and can reach the surface of tumors more easily. The radioactive atom
allows the distribution of the Affibody molecules in the body to be
analyzed by positron emission tomography (PET) imaging.

The research team first used the radiolabeled Affibody molecule to
visualize tumors that expressed HER2 in mice. The mice were injected under
the skin with human breast cancer cells that varied in their levels of
HER2 expression, from no expression to very high expression. After three
to five weeks, when tumors had formed, the mice were injected with the
Affibody molecule and PET images were recorded. The levels of HER2
expression as determined by PET were consistent with the levels measured
in surgically removed samples of the same tumors using established
laboratory techniques.

To determine whether their method could be used to monitor possible
changes in HER2 expression in response to treatment, the team next
injected the Affibody molecule into mice with tumors that expressed very
high or high levels of HER2 and then treated them with the drug 17-DMAG,
which is known to decrease HER2 expression. PET scans were performed
before and after 17-DMAG treatment. The researchers found that HER2 levels
were reduced by 71 percent in mice with tumors that expressed very high
levels of HER2 and by 33 percent in mice with tumors that expressed high
levels of HER2 in comparison with mice that did not receive 17-DMAG. The
researchers confirmed these reductions by using established laboratory
techniques to determine the concentrations of HER2 in the tumors after
they were removed from the mice.

"Our work shows that PET imaging using Affibody molecules was sufficiently
sensitive to detect a twofold to threefold decrease in HER2 expression,"
said senior author Jacek Capala, Ph.D., of NCI's Center for Cancer
Research. "Therefore, PET imaging may provide a considerable advantage
over current methods. Our technique would allow a better selection of
patients for HER2-targeted therapies and also early detection of tumors
that either do not respond to or acquire resistance to these therapies."

"This approach might easily be extended to forms of cancer other than
breast cancer," continued Capala. "Because Affibody molecules may be
selected to target specific cell proteins, similar compounds can be
developed to target proteins that are unique to other types of tumors."

For more information on Dr. Capala's research, please go to



<http://ccr.cancer.gov/staff/staff.asp?profileid=9891>



NIBIB, a component of NIH, is dedicated to improving health by bridging
the physical and biological sciences to develop and apply new biomedical
technologies. Additional information and publications are available at



<http://www.nibib.nih.gov>.



NCI leads the National Cancer Program and the NIH effort to dramatically
reduce the burden of cancer and improve the lives of cancer patients and
their families, through research into prevention and cancer biology, the
development of new interventions, and the training and mentoring of new
researchers. For more information about cancer, please visit the NCI Web
site at



<http://www.cancer.gov>



or call NCI's Cancer Information Service


at 1-800-4-CANCER

(1-800-422-6237)



The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and its
programs, visit



<http://www.nih.gov>



-----------------------



REFERENCE:


Kramer-Marek G, Kiesewetter DO, and Capala J.
HER2 expression changes in breast cancer xenografts following therapeutic
intervention can be quantified using PET imaging and 18F-labelled Affibody
molecules
"J. Nucl. Med." Vol.50, No. 7.




##




This NIH News Release is available online at:
<http://www.nih.gov/news/health/jul2009/nci-01.htm>.




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