The findings, based on animal studies and appearing in today's issue of Clinical Cancer Research, mark the first time arsenic has been used to label antibodies for the detection of tumours.
Dr. Philip Thorpe, professor of pharmacology at UT Southwestern and senior author of the study, helped create the cancer drug called bavituximab, an antibody that homes in on a specific molecular target on the blood vessels that feed tumours. Bavituximab is being tested in clinical trials to treat solid-tumour cancers in combination with chemotherapy.
"While arsenic has been used as a poison for centuries, the dose of arsenic needed for imaging tumours is about one-millionth of that needed to cause toxicity," Dr. Thorpe said.
"Arsenic-labeled bavituximab appears to be safe."
In the study, Dr. Thorpe and his colleagues injected radioarsenic-labeled bavituximab into rats with prostate tumours. When the bavituximab bound to its target on the the tumour blood vessels, the tag-along arsenic created a "hot spot" that researchers then imaged using positron emission tomography methods. The radioactivity levels produced by the arsenic are comparable to those used in standard, routine imaging procedures in humans. The technique allowed them to locate and capture unusually clear images of the tumours. They also discovered that there was little or no detectable uptake of bavituximab by normal organs, including the liver, a common site where drugs become entrapped.
"We hope to use this technique to detect early tumour deposits that are not visible using other imaging techniques," said Dr. Thorpe. "The images we obtain are so clear that we may be able to see secondary tumours that have spread from the original tumour mass and lodged in distant organs."
The forms of arsenic used in the experiments are called radionuclides, which are radioactive versions, or isotopes, of the element. Several radionuclides currently are used in imaging, but many of the isotopes decay, or breakdown, before they reach the target in the body. The slow rate of decay of arsenic isotopes, together with their stable chemistry, allowed the researchers to couple arsenic to bavituximab and obtain images of the tumours for several days after the drug was given. Optimal tumour imaging in humans is often achieved three days or more after a radio-labelled antibody is administered.
"Long neglected as an awkward Cinderella, arsenic has great potential for new imaging agents and therapeutics based on multiple isotopes with diverse useful characteristics," said Dr. Ralph Mason, professor of radiology, director of the UT Southwestern Cancer Imaging Program and one of the study's authors.
Dr. Mason recently received a grant from the Department of Defence Breast Cancer Initiative to investigate whether arsenic could be used to image breast tumours.
