PET Imaging Technology to Improve Cancer Treatment

	A representative [18F]CFA PET image in humans. Arrows indicate liver, lymph nodes, spleen and bone marrow, which express high levels of dCK. Image: UCLA Department of Molecular and Medical Pharmacology

A discovery by UCLA scientists could lead to a new method of identifying cancer patients who have high levels of an enzyme and are more likely to respond to cancer treatments. Decades of significant advances and improvements in positron emission tomography (PET) have led to the detection of an enzyme in humans that plays a significant role in DNA formation. The enzyme, called deoxycytidine kinase (dCK), was previously found to be highly expressed in acute leukemia cells and in activated lymphocytes and controls a critical step in the nucleoside salvage pathway, an important therapeutic and PET-imaging target in cancer.

In a seven-year study, a team of UCLA researchers led by Caius Radu, MD, professor of molecular and medical pharmacology, developed a highly sophisticated PET probe called [18F]CFA that is capable of detecting dCK activity in humans for the first time. “The quality of the images is much better,” Dr. Radu says. “We are able to clearly see tissues, including tumor tissues, with high dCK activity that we haven’t seen before in humans using any of the other probes previously developed for this enzyme.”

PET is a noninvasive imaging technology that uses a radioactive substance, called PET probe, to look for disease in the body, and it also shows how organs and tissues are functioning. Until recently, PET technology was only able to clearly detect dCK in mice due to metabolic instability of the previous probes and cross-reactivity with a dCK-related enzyme in humans. The dCK enzyme plays an integral role in allowing drugs such as clofarabine, cytarabine and fludarabine to treat certain types of leukemia, and others like gemcitabine to treat breast, ovarian, non-small-cell lung and pancreatic cancers.

“This enzyme is essential for the therapeutic activity of an entire class of anticancer drugs and even for some antiviral drugs,” Dr. Radu says. “It can take an inactive drug and activate it. If you trick a cancer cell or virus to activate the drug, it would be toxic for the cancer cell or viral genome.”

Because activated immune cells increase their expression of the dCK enzyme, [18F]CFA could also be used to monitor the effectiveness of immunotherapeutic interventions, Dr. Radu says. The researchers hope to begin clinical trials with the [18F]CFA soon.

“[18F]CFA as a Clinically Translatable Probe for PET Imaging of Deoxycytidine Kinase Activity,” Proceedings of the National Academy of Sciences of the United States of America, April 12, 2016