Positron emission tomography (PET) is a nuclear medicine imaging technique that is used to observe metabolic processes in the body. It locates areas suspicious for cancer because of the increased metabolism of cancer cells. Now, researchers affiliated with the UCLA Jonsson Comprehensive Cancer Center have developed an improvement in the technology that could lead to better treatments for many deadly cancers. The findings were published online on March 28 in the journal Proceedings of the National Academy of Sciences of the United States of America.
The authors of the seven-year study note that the new technology could lead to a new method of identifying cancer patients that express high levels of a certain enzyme and are more likely to respond to cancer treatments. The enzyme, called deoxycytidine kinase (dCK), plays a significant role in the formation of DNA, which carries most of the genetic instructions used in the development, functioning, and reproduction of all known living organisms. The enzyme was previously found to be highly expressed in acute leukemia cells and in activated lymphocytes; it controls a critical step in the nucleoside salvage pathway, an important therapeutic and PET imaging target in cancer.
The research team led by Dr. Caius Radu, MD, a UCLA Jonsson Comprehensive Cancer Center member and a professor in the Department of Molecular and Medical Pharmacology, has developed a highly sophisticated PET probe called [18F]CFA, which is capable of detecting dCK activity in humans for the first time. “The quality of the images is much better,” explained Dr. Radu. He added, “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.”
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 important role in allowing drugs such as Clofarabine, Cytarabine and Fludarabine to treat certain types of leukemia and others such as Gemcitabine to treat breast, ovarian, non-small cell lung and pancreatic cancers. Dr. Radu said, “This enzyme is essential for the therapeutic activity of an entire class of anticancer drugs and even for some antiviral drugs. 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.”
Dr. Radu noted that, because activated immune cells increase their expression of the dCK enzyme, [18F]CFA could also be used to monitor the effectiveness of immunotherapeutic interventions. He and his team hope to begin clinical trials with the [18F]CFA in the near future. They will eventually seek Food and Drug Administration (FDA) approval.