(275a) Estrogen-Loaded X-Ray CT Contrast Agents for Preclinical Detection of ER+ Breast Cancer

Breast cancer is the most common cancer and the 5^th highest cause of cancer mortality. The number is projected to increase 39% by the year 2040. Early detection of the disease is thus highly important. Mammography and X-ray-computed tomography (CT) are considered the most suitable medical imaging methods in terms of patient comfort and cost. Non-invasive disease detection with pronounced signal enhancement at the site of tumor is a great challenge in medicine and allows for condition estimation at early stages. Designing metallic nanoparticle (NP) contrast probes for spectral CT imaging that can be statistically differentiated 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 an X-ray contrast probe that is specifically targeting estrogen receptor positive (ER+) breast cancer cells and tumors, aiming to achieve early disease diagnosis and enhanced CT detection at low NP dosages. Among the 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 and 1.0 g/ mL of soft tissue. Taking advantage of the fact that the X-ray absorption is highly dependent on the K-edge and density of materials, we have synthesized hydrophilic, estradiol-PEG-AuNPs with high delivery inside ER+ breast cancer cells via estradiol-ER interactions and CT contrast comparable to that of iodinated molecules at equal metal basis. Synthesis and characterization of the NPs will be shown, in vitro studies with ER+ breast cancer cells with our NPs and controls, CT studies in solution and cell pellets, as well as results from our first in vivo studies with a relevant animal model, where both active and passive tumor targeting are explored. Our approach combines NP targeting receptor specificity with dual-energy CT (DE-CT) or photon-counting spectral CT (PCD-CT) for tumor and micro-tumor detection.