Arsenic may provide new imaging agent for tumors
Nancy D. Lamontagne
Doctors use methods such as PET, CT, MRI, ultrasound and optical imaging to study tumor development and to see how well therapy is working. Of these techniques, nuclear imaging has the advantage of requiring only low concentrations of tracer/reporter. However, many isotopes now in use decay rapidly, which means that they can’t be used for long-term studies.
Researchers used arsenic isotopes attached to bavituximab (which targets tumor blood vessels) to image tumor-bearing rats with whole-body planar scintigraphy (A). There was an eightfold higher intake of bavituximab (B) than of a control antibody (C). Images reprinted with permission from Clinical Cancer Research.
Researchers at the University of Texas Southwestern Medical Center at Dallas, at Johannes Gutenberg University of Mainz in Germany, at the University of Brussels in Belgium and at the University of Texas at Austin have been experimenting with arsenic isotopes — which are more long-lived than currently used isotopes — to see whether they would be useful for long-term studies. Although arsenic is known as a poison, the amounts used for imaging are about one-millionth the amount of a toxic level, according to lead researcher Philip E. Thorpe of the University of Texas Southwestern Medical Center.
Small-animal PET images taken 48 h after injection of radioarsenic-labeled bavituximab were overlaid on MRI slices (coronal view (A), transaxial view (B)). The arrows show localization of the radioarsenic-labeled bavituximab to the tumor. Sequential tumor slices from the 3-D PET data sets also show tumor localization of bavituximab (C).
In the researchers’ most recent work, they labeled bavituximab with radioactive arsenic isotopes and used the construct to image rats with prostate tumors. Bavituximab is a potential cancer treatment that Thorpe helped create. It is an antibody analog that targets a molecule on blood vessels that feed tumors. When bound to a blood vessel, it alerts the body’s immune system to attack the tumor’s cells. It’s currently being used in combination with chemotherapy in clinical trials on treating solid-tumor cancers.
Autoradiography images of excised tumor sections after 48 h (top row) and 72 h (bottom row) show that the radioarsenic-labeled bavituximab localized to the periphery of the tumor as well as to the entirety of its core.
As described in a paper scheduled for a future issue of Clinical Cancer Research, the researchers found that, when the bavituximab bound to the tumor blood vessels, the attached arsenic could be imaged using PET techniques. The images captured were very clear, and there was little or no detectable uptake of bavituximab by organs without tumors. The slow rate of decay of arsenic isotopes as well as their stable chemistry allowed imaging of the tumors several days after the drug was given. This is important because optimal tumor imaging in humans often is three days after the drug is administered, when free antibodies have had time to clear the body.
The researchers concluded that radioarsenic-labeled bavituximab shows promise as a vascular imaging agent for human tumor detection.
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