Variable Activation of the DNA Damage Response Pathways in Patients Undergoing Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging

Won Hee Lee, PhD, Patricia Nguyen, MD, Shijun Hu, PhD, Grace Liang, BS, Sang-Ging Ong, PhD, Leng Han, PhD, Veronica Sanchez-Freire, PhD, Andrew S. Lee, PhD, Minal Vasanawala, MD, George Segall, MD and Joseph C. Wu, MD, PhD

Background—Although single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) has improved the diagnosis and risk stratification of patients with suspected coronary artery disease, it remains a primary source of low-dose radiation exposure for cardiac patients. To determine the biological effects of low-dose radiation from SPECT MPI, we measured the activation of the DNA damage response pathways using quantitative flow cytometry and single-cell gene expression profiling.
Methods and Results—Blood samples were collected from patients before and after SPECT MPI (n=63). Overall, analysis of all recruited patients showed no marked differences in the phosphorylation of proteins (H2AX, protein 53, and ataxia telangiectasia mutated) after SPECT. The majority of patients also had either downregulated or unchanged expression in DNA damage response genes at both 24 and 48 hours post-SPECT. Interestingly, a small subset of patients with increased phosphorylation had significant upregulation of genes associated with DNA damage, whereas those with no changes in phosphorylation had significant downregulation or no difference, suggesting that some patients may potentially be more sensitive to low-dose radiation exposure.
Conclusions—Our findings showed that SPECT MPI resulted in a variable activation of the DNA damage response pathways. Although only a small subset of patients had increased protein phosphorylation and elevated gene expression postimaging, continued care should be taken to reduce radiation exposure to both the patients and operators.