Via their cognate receptors, chemokines orchestrate the migration and activation of various classes of immune cells and, thus, play a central role in the pathogenesis of cellular inflammation that underlies a host of common diseases such as atherosclerosis, Alzheimer’s disease, various forms of inflammatory lung disease and numerous cancers. As a consequence, there is intense interest in clarifying the roles of various chemokines and their receptors in human diseases and in the development of novel therapeutics and imaging approaches directed at this system. Currently, it is unclear whether broad spectrum or individually targeted therapeutics should be employed. Consequently, it is also uncertain whether imaging a panel of key chemokine receptors or targeting a specific receptor would be most useful as a diagnostic agent to determine disease activity, progression or assess drug treatment efficiency. However, what is clear is that the chemokine receptor imaging agents are underdeveloped. Given the constant evolution in human disease pathogenesis, it is critical the imaging methods that are developed are widely applicable in humans.
Building upon our expertise in synthesizing various chemokine receptor targeted PET radiotracers for vascular injury, atherosclerosis and cancer applications, our objective is to first translate a broad spectrum chemokine receptor imaging agent using viral inflammatory macrophage protein-II ([64Cu]-DOTA-vMIP-II) to determine the overall expression of chemokine receptors in head and neck cancer patients and then focus a chemokine CC receptor 2 (CCR2) targeted PET radiotracer using a peptide ECL1 inverso ([64Cu]-DOTA-ECL1i).
[64Cu]-DOTA-vMIP-II Imaging Head & Neck Cancer in Patient Derived Xenograft Model