New probe for PET scanning enables monitoring of the immune system
David L. Shenkenberg
The immune system destroys bacteria, viruses and many other objects that otherwise would harm the body. However, in patients with cancer, it usually does not annihilate the tumor. Recent clinical studies have shown that it can be trained to eliminate the tumor; however, clinical researchers currently can monitor patients’ immune systems only indirectly.
A probe for PET scanning developed by Dr. Caius G. Radu and others at the University of California, Los Angeles (UCLA), may change that. It also could help clinical researchers monitor how the immune system turns against healthy tissues in diseases such as autoimmunity.
As with MRI and CT, PET scanning shows a 3-D view of a patient. However, MRI and CT show all of the organs and bones, whereas only certain regions of the body labeled by the probe are displayed clearly in a PET scan. They show up onscreen as hot spots of reds, yellows, greens, blues and purples. These are false colors, depending upon how much the probe is taken up by cells in those body regions. Miniaturized PET scanners are available for research studies with laboratory animals such as mice and rats.
Although PET is popular, almost 100 percent of PET scans use just one probe, called FDG, a modified version of glucose. It is useful for labeling fast-growing cancers, active regions of the brain and anything else that metabolizes glucose quickly. However, it does not provide specific enough information for some applications, Radu said.
So the researchers developed a new probe. To have the probe label the immune system, it had to be a chemical compound that the immune system would take up. They used a new chemistry strategy to find such a compound. To their surprise, they rediscovered the commonly used chemotherapy drug gemcitabine. This drug acts on the DNA salvage pathway, which recycles DNA. This pathway is active in immune cells, which readily take up the probe as a result.
This is how an autoimmune disorder in a mouse looks with the new probe. Percentage ID/g = percentage of injected dose of radioactivity per gram of tissue.
To develop a new PET imaging probe, the researchers modified gemcitabine to enable the addition of the radioactive label. In general, adding the PET radioisotope to the probe has been a big challenge for creating new PET tracers, Radu said.
In studies with mice, the new probe labeled regions of the body where the immune system is active, including the thymus, spleen and lymph nodes. Preliminary clinical studies will begin soon. “We have to demonstrate first in a very small group of patients that the probe has potential,” Radu said.
He pointed out that the immune response to cancer treatment as shown by the new PET probe could reveal whether or not treatment is working within a week or two. Currently, MRI and CT are used to determine whether the tumor is growing or shrinking in response to treatment, but it takes a month or even longer before a noticeable change in tumor size can be seen. By cutting the time to just a week or two, PET using existing probes and the newly developed tracer not only would help spare the patient unnecessary treatment but also reduce the associated expense.
Radu joined the faculty of UCLA after receiving his medical degree in Romania and completing a stint at the University of Texas Southwestern in Dallas. He was joined on the paper by several others, including his “mentor” Dr. Owen N. Witte and Dr. Michael E. Phelps, the single person most often credited as the inventor of PET.
Nature Medicine, Advance Online Publication, June 8, 2008, doi: 10.1038/nm1724.
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