Optimization of macrophage-targeted nanoparticles for positron emission tomography imaging in cancer
Mentor: Ralph Weissleder, MD (MGH)
Macrophages play a critical role both in normal physiology (tissue resident macrophages, TRM) and in disease states (for example tumor associated macrophages, TAM). Understanding macrophage relative numbers, distribution profiles, and mobilization and flux rates across different diseases and normal physiologic conditions could enhance the effects of macrophage-targeted therapies. The Weissleder Laboratory has developed macrophage-specific nanomaterials allowing the visualization of macrophage biology in vivo. The first generation of these nanoparticles was labeled with the radioisotope zirconium-89 (89Zr), which has a half-life of 3.27 days. These materials have been used for positron emission tomography (PET) imaging in murine models of cancer, myocardial infarction and atherosclerosis, all diseases where inflammation has been associated with adverse prognosis. To optimize the nanoparticles for clinical translation, we will explore radiolabeling with fluoride-18 (18F), the most widely used and commonly available PET isotope. Our goal is to develop a rapid, efficient, fully automated radio-synthesis of 18F-labeled nanoparticles.
Systemic administration of 89Zr-labeled nanoparticles allows for macrophage specific PET-CT imaging of bilateral flank tumors (CT-26, colon carcinoma cells) in mice. Imaging was performed 24 hours post injection of nanoparticles. Source: