(269b) "Ringing" Breast Tumors with Ligand-Specific X-Ray Contrast Agents and Spectral CT

X-ray-computed tomography (CT) is considered one of the powerful diagnostic techniques for preclinical and clinical studies due to deep tissue penetration, high resolution, cost effectiveness, rapid scan times and patient comfort. Non-invasive disease detection with pronounced signal enhancement at the site of injury is a great challenge in medicine and allows for condition estimation in early stages. Designing metallic nanoparticle (NP) contrast probes for spectral CT imagingthat can be statistically discriminated from biological fluids, tissue, and bone (a property that is impossible to achieve with conventional CT), and are empowered by molecular recognition, aligns towards that direction. Our Team (UML-Chemistry / UMMS-Radiology) is developing X-ray contrast probes based on molecular recognition for breast cancer cells, aiming to achieve early disease diagnosis and enhanced detection at low NP dosages. Among our recent findings is the ability to detect breast tumors in vivo for up to 21 days with <0.5 mg of Au. Our approach combines NP targeting specificity with dual-energy CT or photon-counting spectral CT (PCD-CT),a state-of-the-art form of spectral CT that allows for visualization of tissue composition based on intensity of signal, which is dictated by atomic number and density of contrast materials, and thus is enhanced by metallic NPs. Au offers significant advantages towards materials differentiation since its K-edge is 81 vs. 4 keV of Ca, while its density is 19.6 vs. 1.6 g/mL of Ca. Since X-ray absorption is highly dependent on K-edge and density of materials, we synthesize Au-based nano-contrast agents with high affinity for breast cancer cells and CT contrast comparable/higher to FDA-approved iodinated molecules at equal metal basis.Our materials are tested in vitro as well as in vivo with relevant animal models. The most recent findings on animal studies will be highlighted.