(584ba) Multimodal Contrast Agent for Prostate Cancer Diagnosis

One of the most prominent issues that have arisen due to increased life expectancy in developed countries is the increased rate of prostate cancer. Prostate cancer is currently the most common type of cancer in men and is the second leading cause of cancer related deaths. Despite decades of effort in the fight against cancer, current diagnostic techniques are inaccurate and therapies for prostate cancer are often ineffective. Nanomedicine, however, has the potential to solve the current shortcomings of prostate cancer treatments.

Much of our failure in treating cancer stems from the fact that, despite all the knowledge gained, still very little is known about the factors affecting cancer progression. Recently, there has been a great interest in combining data from multiple diagnostic modes – for example, the physiological information from magnetic resonance imaging (MRI) and metabolic data from positron emission tomography (PET) – to improve our understanding of cancer growth. In response to these developments, this project looks to develop multi-modal (MRI/PET) contrast imaging agents that would provide qualitative anatomical information and quantitative data on the biological activities within tumor lesions. We use magnetic iron oxide nanoparticles as our multifunctional system due to their intrinsic diagnostic capabilities as MRI contrast agents and the ability to add functionalities, through appropriate surface modifications, to include targeting moieties, fluorescence dyes and radioactive agents. In this work, we demonstrate the successful synthesis and fractionation of iron oxide nanoparticles that can be used as multimodal imaging agents. Each fractionated size distribution was then used in several in vitro experiments to determine what effect nanoparticle size has on particle size stability, protein binding, and macrophage uptake, which all affect in vivo pharmacokinetics and biodistribution of the nanoparticles. The results of this work allow us to identify an optimal size to be used in vivo. Moving forward, peptides identified thorough phage display technology will be investigated as viable moieties to target molecules specific to prostate cancer and to monitor the proteolytic activity in the tumor’s microenvironment. These targeted contrast agents can then be utilized to optimize nanomedicines for cancer diagnosis and therapy.