“A Personalized Medicine Approach for Prostate Cancer Using Quantitative Molecular Imaging”
Christian Konopka, a Ph.D. student in bioengineering and a member of Beckman’s Multimodal Vascular Imaging Group
Prostate cancer (PCa) is the leading cause of cancer-related death in men, however the majority of newly diagnosed PCa is low-grade. Therefore, many patients forego initial treatment for active surveillance (AS), which utilizes screening tests that are often insufficient in predicting when life-saving intervention is necessary. Therefore, there is tremendous need for a method of monitoring PCa in patients undergoing AS. Presence of the receptor for advanced glycation end-products (RAGE) is associated with all signature characteristics of prostate cancer development, and increased RAGE levels in conjunction with its ligands predict poor prognosis. Therefore, to address this problem, we established a preclinical multimodal imaging strategy targeted to assess RAGE levels in PCa. We developed RAGE-targeted nanoparticles for both fluorescence and PET imaging. Cell culture studies confirmed the nanoparticle’s high affinity and specificity for RAGE. RAGE expression and binding of the RAGE-targeted nanoparticle was visualized in murine PCa xenograft models as well as human PCa biopsy samples. The analysis of PET-CT images revealed favorable kinetics, rapid blood clearance, and a non-homogenous uptake of the tracer in tumors. Uptake values varied with tumor size and type. Human biopsy samples all demonstrated increased levels of RAGE protein, and the severity of pathological tumor grading correlated with increased RAGE levels. This study demonstrates that this probe can assess RAGE in PCa tumors and that tumors exhibit varying degrees of RAGE expression and imaging features. Given the correlation of RAGE protein levels with tumor grading it is likely that this RAGE-targeted imaging strategy could significantly improve upon the current methods for monitoring and managing therapies for PCa patients.
“Investigating Excited State Electronic Structure and Dynamics of Nanomaterials"
Alison Wallum, a Ph.D. student in chemistry and a member of Beckman's Nanoelectronics and Nanomaterials Group
Traditionally, studies surrounding excited states of materials are carried out with spectroscopic techniques that characterize bulk behavior. Standard imaging techniques alternatively provide spatial information about materials, however they generally only probe ground-state characteristics. In an effort to spatially resolve excited state characteristics of nanomaterials, our group has developed an imaging technique known as single-molecule absorption scanning tunneling microscopy (SMA-STM). This seminar will outline how SMA-STM allows us to probe the change in electronic density associated with excitation, creating an image that maps the excited state electronic structure of nanomaterials on the sub-nm scale. Our group uses this technique to investigate the excited state structure of nanomaterials including carbon nanotubes and quantum dots in an effort to inform the use of these materials in molecular electronics. Alongside this, we are able to map energy transfer dynamics between clusters of these nanomaterials. Recently, we have imaged and modeled the behavior of excited quantum dots in close proximity to carbon nanotubes. Results show a distance-dependent transverse polarization of nanotubes relevant to applications of carbon nanotubes in field effect transistors. Moving forward, this technique will be used to study the electronic and excited state properties of carbon nanothreads.
