Chemotherapeutic drugs are toxins for killing tumor cells, but their efficacy is often limited by the tolerance ceiling of normal tissues. A survey of systemic toxicity will provide valuable information on a new drug candidate for pharmaceutical development, and on the therapeutic regimen for existing drug combinations for each patient. The overall goal of this project is to develop and validate whole-body apoptosis imaging as a new approach for characterizing the systemic toxicity profile of anticancer drugs. Apoptosis is an important manifestation of toxicity-induced tissue injuries. A whole-body scan, which we call ToxScan, detects tissue injuries systemically, in terms of a toxicity profile in response to the drug. We use a radiopharmaceutical, 99mTc-Duramycin, which detects exposed phosphatidylethanolamine in dead and dying cells. The imaging agent has binding affinity/specificity like an antibody yet clearance kinetics of a peptide. It is thus uniquely suitd for whole-body imaging applications. Our central hypothesis is that a systemic toxicity profile reflects the individual susceptibility to anticancer treatment. The scan provides indices for drug tolerance, and a prognostic indicator for chronic adverse effects. In preliminary studies, we demonstrated the sensitivity of whole-body 99mTc-Duramycin scan by detecting cell death in multiple tissues after a single clinically relevant dose of Doxorubicin. Whole-body apoptosis scan also revealed individualized response to the same therapeutic regimen. Single-and multi-organ indices for tissue injury are being derived for diagnostic and prognostic purposes. The evaluation of toxicity in such fashion will significantly accelerate the development of new anticancer drugs and new combination treatments. Ultimately, this approach will benefit oncology patients by optimizing therapies on a personalized basis.

Public Health Relevance

We propose to develop and validate a whole-body apoptosis imaging technique for assessing systemic toxicity induced by anticancer treatment. This approach provides a diagnostic indicator for drug tolerance and prognostic index for chronic effects. It will help make pharmaceutical development a more efficient process and ultimately benefit clinical oncology by optimizing cancer treatment on a personalized basis.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Menkens, Anne E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northwestern University at Chicago
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Johnson, Steven E; Ugolkov, Andrey; Haney, Chad R et al. (2018) Whole-body Imaging of Cell Death Provides a Systemic, Minimally Invasive, Dynamic, and Near-real Time Indicator for Chemotherapeutic Drug Toxicity. Clin Cancer Res :
Hou, Songwang; Harper, Paul E; Bardin, Nathalie et al. (2017) The outcome of ELISA for antiphosphatidylethanolamine antibodies is dependent on the composition of phosphatidylethanolamine. J Immunol Methods 440:27-34
Zang, Shiming; Shao, Guoqiang; Cui, Can et al. (2017) 68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients. Oncotarget 8:12247-12258
Audi, Said H; Jacobs, Elizabeth R; Zhang, Xiao et al. (2017) Protection by Inhaled Hydrogen Therapy in a Rat Model of Acute Lung Injury can be Tracked in vivo Using Molecular Imaging. Shock 48:467-476
Zhao, Ming (2016) Innovative reporter gene imaging techniques making inroads to biology. Cardiovasc Res 112:617-618
Luo, Rui; Niu, Lei; Qiu, Fan et al. (2016) Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT. Mol Imaging 15:
Ke, Ke; Strango, Zachariah I; Harper, Paul E et al. (2016) Influence of Phosphatidylethanolamine Concentration and Composition on the Detection of Antiphosphatidylethanolamine Antibodies by ELISA. J Clin Lab Anal 30:689-96
Hou, Songwang; Johnson, Steven E; Zhao, Ming (2015) A One-Step Staining Probe for Phosphatidylethanolamine. Chembiochem 16:1955-1960
Audi, Said H; Jacobs, Elizabeth R; Zhao, Ming et al. (2015) In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-duramycin. Nucl Med Biol 42:46-52