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On Target - Cancer Treatment Heats Up

Winter 2009

Cancer Treatment Heats Up

Date: December 1, 2009

Meet Robert Ivkov, Ph.D., visiting assistant professor in the Division of Molecular Radiation Sciences of the Department of Radiation Oncology and Molecular Radiation
Sciences at Johns Hopkins. With a background in physical chemistry and materials
science, he is an expert in the field of nanoparticles, with a particular interest in magnetic
nanoparticles. He brings his unique talents to the multidisciplinary team that makes Radiation Oncology and Molecular Radiation Sciences outstanding in the field of cancer
research and treatment.

Dr. Ivkov’s work builds on previous research, which has shown that heat sensitizes
cancer cells, making them easier targets for chemotherapy and radiation. Until now, applying this knowledge to create successful treatment options for patients has been difficult.

The difficulty has been largely a technical challenge: how to heat cancerous tissue
without harming healthy tissue, and how accurately to measure how much heat is
absorbed by the cancer. If a doctor is unable to deliver heat selectively to the cancer or to
know precisely how much heat is absorbed by the cancer, it is very difficult to provide treatment plans that will produce consistent and predictable results for the patient.

In general, cancer cells are particularly susceptible to changes in temperature. Increasing
the temperature of a cancer cell from 37°C to 43°C for a sufficient period of time can
make the cancer very sensitive to radiation or chemotherapy. This represents a very exciting opportunity to make already effective treatments even more effective and, potentially, less likely to produce unwanted side effects.

Dr. Ivkov and his team are now showing that they can cause cancer-specific heating
by putting magnetic nanoparticles into the cancer and exposing these nanoparticlecontaining cancers to an alternating magnetic field, which heats the particles.

The magnetic nanoparticles can either be injected directly into the cancerous tissue, or, can accumulate in the cancer, after intravenous injection, if they have first been coated with suitable targeting molecules that take them directly to cancer cells. In this manner, the cancer is treated locally, at the cellular level, and, by targeting the nanoparticles only to cancer cells, the damage to healthy tissue is minimized.

In some of his early work, Dr. Ivkov used sugar polymer-coated nanoparticles that contained small amounts of iron oxide crystals. The sugar polymer coating was chosen to allow the nanoparticles to circulate quickly through the bloodstream to the cancer.

About two or three days after injection into mice with human breast tumor xenografts,
Dr. Ivkov applied the alternating magnetic field, which heated the iron oxide, which, in turn, raised the temperature inside the cancer cells. Dr. Ivkov observed that this
increased temperature was enough to reduce tumor growth. He posits that the higher
temperature should make the tumors “exquisitely susceptible to chemotherapy and radiation,” without causing significant side effects in the mice.

Dr. Ivkov chooses to explore iron oxide because it is ubiquitous in nature, being found in both migratory birds and humans, and because it may be the lowest risk to patients of all the possible nanoparticle materials that can be injected. As Dr. Ivkov points out, the fact that these coated, iron oxide nanoparticles are already being used safely, as contrast agents to increase the precision of detecting abnormalities by MRI, makes their use much more attractive to explore their efficacy to kill cancer.

He feels it is important to focus on developing the basic technology, heating the nanoparticles with alternating magnetic field devices, as a more direct route to clinical
trials, as well as a way to determine the likelihood of success for nanoparticle technologies
in cancer care. Presently, Dr. Ivkov and his research team are refining the choice of nanoparticles and working out details of heating the particles in both cells and animals
bearing human tumors. This work directly supports the goal of the first human clinical
trial, in which the heating component of nanotechnology will be integrated with the
radiation treatment.

In theory, an MRI scan would reveal the location of iron oxide-impregnated cancer
cells presently undetectable by routine scanning methods. These nanoparticles would
then be heated right before radiation or chemotherapy is delivered, thereby increasing
the effectiveness of each.

In keeping with the Johns Hopkins philosophy of a multidisciplinary team effort, Dr.
Ivkov works on this project with different collaborators who possess complementary expertise and knowledge. Dr. Ivkov particularly notes his collaboration with Shawn Lupold, Ph.D., assistant professor in the Department of Urology. Dr. Lupold is an expert in molecular targeting and is primarily responsible for helping Dr. Ivkov with designing molecules to direct the nanoparticles to cancer cells. Dr. Ivkov is also pursuing work on the blood/brain barrier with fellow Radiation Oncology and Molecular Radiation Sciences
assistant professor Eric C. Ford, Ph.D., whom we introduced in our inaugural issue
of On Target.

Until two years ago, Dr. Ivkov’s nanotechnology did not exist. Now, the data Dr.
Ivkov and his colleagues are collecting in the laboratory is moving the research toward the
clinic; from the theoretical to the reality of treatment in the continuum of patient care
that is the standard for the Department of Radiation Oncology and Molecular Radiation
Sciences at Johns Hopkins.

Articles in this Issue

Letter From The Chairman

Cancer Treatment Heats Up

Cancer Damage Control

The Scale of Cancer Treatment

Zooming in on Breast Cancer