It is known that monocytes and their lineage-descendant macrophages play critical roles in the initialization and progression of inflammatory diseases such as cardiovascular disease, neurodegenerative diseases and cancer. Of various chemokine and chemokine receptor axes, the CCL2/CCR2 pair is of particular interest owing to their role in regulating monocytes migration and recruitment to the sits of inflammation, which makes CCR2 a promising target for both diagnosis and treatment of inflammatory diseases including rheumatoid arthritis, asthma, multiple sclerosis, neuropathic pain, and atherosclerosis. Therefore, the non-invasive imaging of CCR2 will be highly attractive for early detection, monitoring the progression, and guiding the CCR2 inhibitor treatment.
The aim of this proposal is to develop the first CCR2 PET imaging agent and validate the probe sensitivity and specificity with collaborative projects (CPs). To further improve the imaging specificity and sensitivity and enhance the dissemination capability when necessary using 68Ga radiolabeling or through a multivalent nanoplatform which could be clear via renal system and degraded in vivo. We will also facilitate the dissemination by developing a microfluidics kit device and provide to the CPs and service projects to further test the agents developed in this project. We anticipate that a lead compound for sensitive and specific detection of CCR2 will be identified for future translation.