Development of a novel PET-based duramycin probe for cell death imaging in tumors.

Cell death is a fundamental biological process. As different therapies may result in activation or inhibition of cell death, there is a need for imaging techniques that can identify cell death during patient treatment. The development of molecular probes targeting cell death biomarkers are key. The exposure of phosphatidylethanolamine (PE) in the cell membrane is an important biomarker for cell death. Specific in vivo positron emission tomography (PET) imaging of PE could therefore aid in the assessment of early response to cancer therapy, preventing exposure of patients to needless toxicity. Duramycin is a small peptide that binds to PE with high affinity and selectivity. The aim of the current work is the development of [18F]duramycin as a novel radiotracer for noninvasive PET imaging of cell death. Following optimization of radiochemistry, the tracer will be characterized to assess cell death binding and target selectivity, stability and pharmacokinetic behavior. Clinical applicability of the probe for therapy response assessment will be evaluated in well characterized cancer xenograft models treated with regorafenib, a multi-kinase inhibitor.

Keywords:CELL DEATH, MOLECULAR IMAGING, TUMOR IMAGING, SMALL PEPTIDES

Disciplines:Medical imaging and therapy, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Nuclear imaging, Cell death, Cancer biology