In two separate studies of the uptake of boronophenylalanine by malignant brain cells, an American group led by Subhash Chandra, Ph.D., has found that the dose currently favored by clinical researchers is not high enough to target cancer cells effectively. Both with rats and with cultured human tumor cells, the infusion time necessary for adequate uptake of drug was six hours in contrast to the standard duration of one to two hours.

"Different models showing the same thing -- I think this is what gives the strength to this study," says Chandra.

To track the uptake and handling of the drug within brain cells, the researchers used an imaging technique known as subcellular secondary ion mass spectrometry. The technique yields three-dimensional images of ions emitted from a sample. The sensitivity of the technique is so high that it can distinguish between different isotopes. It is extremely well suited to cancer research because chemotherapeutic agents can be tagged with isotopes that will serve as markers when the patient's brain is imaged with mass spectrometry.

Boronophenylalanine is used in an experimental treatment for glioblastoma, which is diagnosed in about 17,000 people annually in the United States. In the treatment, called boron neutron capture therapy, patients are given a drug that contains an isotope of boron attached to an amino acid, and the agent is taken up into malignant cells at a rate three to four times that of the uptake by normal brain tissue.

A beam of low-energy neutrons is then directed at the patient's brain. When a boron atom is hit by a neutron, it captures the neutron and undergoes nuclear fission, releasing two smaller particles. These particles travel 5 to 10 microns -- approximately the width of a cell -- before coming to rest, destroying the tumor cells through which they pass.

Although this form of combined drug and radiation therapy has been moderately successful at treating tumors in clinical trials, small invasive cell clusters beyond the main tumor mass have proved resistant to treatment, taking up lesser amounts of drug than cells in the primary tumor. The new research indicates that with a longer infusion time, drug levels in the outlying cells could approach those in the main tumor mass.

As a result of the current research, Studsvik Medical, a research company in Sweden, has begun clinical trials featuring longer infusions of the drug with the aim of improving the success of the therapy.