Cancer cells consume a large amount of oxygen to produce energy to maintain their proliferative status and require a constant supply of new DNA. Nuclear bases made in cancer cells for DNA replication are under oxidative stress and tend to be damaged much more frequently than those found in normal cells. Dysfunctional redox regulation and increased reactive oxygen species (ROS) in cancer cells cause oxidative damage either directly or indirectly to DNA. Upregulation of MTH1, an oxidized purine nucleoside triphosphatase that specifically hydrolyzes oxidized purine nucleoside triphosphates, occurs in various cancers to repair oxidized DNA and suppress the accumulation of oxidatively damaged nucleic acids. ROS causes cellular dysfunctions such as cell death and mutagenesis by exerting oxidative damage to lipids, proteins, and nucleic acids in living cells. Oxidative damage to nucleic acids can potentially alter nuclear and mitochondrial DNA. In vivo measures of these processes could provide a critical metric of disease progression and a target for drug engagement. MTH1 has been reported to be a crucial enzyme in cancer proliferation and resistance to cancer therapy. This talk will highlight the development and validation of MTH1 radiotracers for imaging oxidative DNA stress in cancer.