Capturing minute changes in DNA could aid early detection of breast cancer

Targeting oncogene-driven activation of DNA damage could be an effective way to tap into the earliest stages of cancer development, or tumorigenesis. An investigative molecular imaging agent was able to do just that in a preclinical Oxford University study published ahead of print Nov. 13 in the Journal of Nuclear Medicine.

A team of researchers including Bart Cornelissen, PhD, from the department of oncology at the Oxford Institute for Radiation Oncology, United Kingdom, assessed In-111 anti-gH2AX antibody united with a peptide called the transactivator of transcription (TAT) to see if it could effectively image the phosphorylated histone H2A variant H2AX, gamma-H2AX—basically a protein that signals DNA damage.

“The DNA damage response (DDR) is a highly regulated cellular process that follows exposure to ionizing radiation and other genotoxic insults,” wrote Cornelissen et al. “The DDR is activated during the earliest stages of cancer development, when it is triggered by the onset of oncogenic stress.”

For this study, the researchers evaluated the agent in SPECT imaging of animal models of breast cancer and compared them to MR images to see if In-111 anti-gH2AX antibody provided any indication of tumorigenesis. Tissue models also were immunostained for gamma-H2AX. Results showed that H2AX was over-expressed in developing tumor tissues.

Repeated SPECT imaging showed a 2.5-fold increase in In-111-anti-gamma-H2AX-TAT accumulation in the mammary tissues of the models compared to controls. The median time it took to detect cellular hyperplasia using the SPECT protocol was 96 days, whereas it took 120 days with dynamic contrast-enhanced MRI and 131 days with tissue palpation.

“The approach of DNA damage imaging has potential applications in the early detection of cancer and screening cancer-prone individuals,” the researchers concluded. “Also the ability to image the DDR noninvasively would enable the response to DDR-targeted drugs to be monitored and might be useful in the development of cancer prevention strategies.”

Due to the ubiquitous nature of DDR activation across tumor types, this concept could potentially be translated for the detection of a variety of cancers. Further study and regulatory approval would be required for this application to reach the clinic.