Image by Jens Langner
A PET probe known as [18F]CFA could be used to aid the treatment of leukemias and other cancers, according to research published in PNAS.
Investigators say [18F]CFA can detect the activity of deoxycytidine kinase (dCK) in humans more effectively than existing probes.
dCK is a rate-limiting enzyme in the cytosolic deoxyribonucleoside salvage pathway and is considered an important therapeutic and PET-imaging target in certain cancers.
Research has shown that dCK is highly expressed in acute leukemia cells and activated lymphocytes. And the enzyme plays an integral role in allowing drugs such as clofarabine, cytarabine, and fludarabine to treat certain leukemias.
“This enzyme is essential for the therapeutic activity of an entire class of anticancer drugs and even for some antiviral drugs,” said study author Caius Radu, MD, of the University of California, Los Angeles.
“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.”
Until recently, PET technology was only able to clearly detect dCK in mice due to the metabolic instability of the available probes and cross-reactivity with a dCK-related enzyme in humans.
However, Dr Radu and his colleagues showed that [18F]CFA can clearly detect dCK in humans.
The team found that [18F]CFA accumulation in leukemia cells correlated with dCK expression, and they were able to inhibit [18F]CFA accumulation with a dCK inhibitor.
Experiments with [18F]CFA PET/CT in humans showed probe accumulation in tissues with high dCK expression, such as hematopoietic bone marrow and secondary lymphoid organs.
“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,” Dr Radu said.
He added that, since activated immune cells increase their expression of dCK, [18F]CFA could also be used to monitor the effectiveness of immunotherapeutic interventions.
The investigators hope to begin clinical trials with [18F]CFA in the near future.
Dr Radu and his team invented [18F]CFA and its analogs, which were patented by the University of California and have been licensed to Sofie Biosciences, a company founded by Dr Radu and his team. The University of California also patented additional intellectual property for small-molecule dCK inhibitors.
