UCLA researchers in the David Geffen School of Medicine Division of Pulmonary and Critical Care Medicine have developed a novel use of the positron emission tomography (PET) tracer [18F]FBnTP to guide the delivery of mitochondrial complex I inhibitors for the treatment of lung cancers.
BACKGROUND:
The mitochondria are essential regulators of cellular energy and metabolism and they play a critical role in sustaining growth and survival of cancer cells. Mitochondria are essential for tumor initiation and maintenance. Previous study showed that loss of mtDNA suppressed tumor cell growth in cell culture and xenografts. However, the oxidative mitochondrial metabolism in cancer remains elusive, because the majority of studies have been performed in vitro in cell culture models. Understanding how oxidative mitochondrial metabolism supports tumor growth will provide new insights into cancer treatments.
INNOVATION:
Dr. David Shackelford who is in the David Geffen School of Medicine Division of Pulmonary and Critical Care Medicine and his colleagues have developed a novel use of the positron emission tomography (PET) tracer [18F]FBnTP to guide the delivery of mitochondrial complex I inhibitors for the treatment of lung cancers. [18F]FBnTP PET is able to measure mitochondrial membrane potential and complex I activity in lung tumor cells. Lung tumors with high uptake of the [18F]FBnTP tracer are dependent on mitochondrial complex I activity and thus sensitive to small molecule complex I inhibitors. Using [18F]FBnTP PET imaging, the researchers were able to successfully identify lung tumors that are sensitive to complex I inhibitors such as metformin, phenformin, IACS-01759 and rotenone. Therefore, [18F]FBnTP PET imaging on lung cancer patients allows the identification of tumors with complex I-dependent metabolism so that they can be precisely treated using complex I inhibitors.
POTENTIAL APPLICATIONS:
• Cancer treatment
ADVANTAGES:
• PET-imaging guided targeted therapy
• Metabolic stratification of tumors susceptible of mitochondrial complex I inhibitors
DEVELOPMENT-TO-DATE:
The study has been validated in the mouse model.