A
single compound with dual function?the ability to deliver a diagnostic
and therapeutic agent?may one day be used to enhance the diagnosis,
imaging and treatment of brain tumors, according to findings from
Virginia Commonwealth University and Virginia Tech.
Glioblastomas
are the most common and aggressive brain tumor in humans, with a high
rate of relapse. These tumor cells often extend beyond the well-defined
tumor margins making it extremely difficult for clinicians and
radiologists to visualize with current imaging techniques. Researchers
have been investigating enhanced methods of attacking these cells in
order to possibly delay or prevent brain tumor relapse.
In
a study published in the August issue of the journal Radiology, the
research team led by Panos Fatouros, Ph.D., a former professor and chair
of the Division of Radiation Physics and Biology in the VCU School of
Medicine who retired in 2010, demonstrated that a nanoparticle
containing an MRI diagnostic agent can effectively be imaged within the
brain tumor and provide radiation therapy in an animal model.
The
nanoparticle filled with gadolinium, a sensitive MRI contrast agent for
imaging, and coupled with radioactive lutetium 177 to deliver
brachytherapy, is known as a theranostic agent?a single compound
capable of delivering simultaneously effective treatment and imaging.
The lutetium 177 is attached to the outside of the carbon cage of the
nanoparticle.
“We
believe the clustering properties of this nanoplatform prolong its
retention within the tumor, thereby allowing a higher radiation dose to
be delivered locally,” said Michael Shultz, Ph.D., a research fellow in
Fatouros’ lab in the Department of Radiology in the VCU School of
Medicine.
“This
theranostic agent could potentially provide critical data about tumor
response to therapy by means of longitudinal imaging without further
contrast administration,” said Fatouros.
A
nanoparticle called a functionalized metallofullerene (fMF), also known
as a “buckyball,” served as the basis of this work and was created by
study collaborator, Harry Dorn, Ph.D., a chemistry professor at Virginia
Tech, and his team. In 1999, Dorn and his colleagues were able to
encapsulate rare earth metals in the hollow interior of these
nanoparticles that can easily be recognized by MRI techniques.
“Although
this is a limited animal study, it shows great promise and hopefully
this metallofullerene platform will be extended to humans,” said Dorn.
Fatouros,
who is the corresponding author on the study, Shultz and Dorn
collaborated with John D. Wilson, Ph.D., associate professor in the VCU
Department of Radiology; Christine E. Fuller, M.D., professor and
director of neuropathology and autopsy pathology at VCU; and Jianyuan
“Jason” Zhang, a graduate student in chemistry at Virginia Tech from
Beijing, China.
The
study was funded by grants to Fatouros from the National Institutes of
Health’s National Cancer Institute, and to Dorn from the National
Science Foundation.
http://www.news.vcu.edu/news/Researchers_Develop_and_Test_New_Molecule_as_a_Delivery_Vehicle