Engineering nanoparticle probes for detecting disease and monitoring therapy with computed tomography

R.K. Roeder, T.E. Curtis, C.J. Evans, T.A. Finamore, L. Li, T.L. McGinnity, P.D. Nallathamby
University of Notre Dame,
United States

Keywords: nanoparticle probes, disease detection


X-ray computed tomography (CT) provides non-invasive, three-dimensional, anatomic imaging at high spatial resolution and relatively low cost for clinical diagnostic imaging, but is limited by the lack of molecular imaging capabilites. However, emerging photon-counting spectral CT systems can enable quantitative multi-material decomposition. Therefore, we are investigating nanoparticle imaging probes engineered to enable quantitative molecular imaging with both conventional CT and photon-counting spectral CT. Nanoparticles are designed for biocompatibility, strong X-ray contrast, multi-agent and multi-modal imaging, and molecular surface modification for colloidal stability and drug delivery. For example, gold nanoparticles have been engineered to target breast microcalcifications and tumor cell populations overexpressing biomarkers (HER2+) for improving the sensitivity and specificity of detecting breast cancer, even in the presence of dense breast tissue. Gold nanoparticles were also covalently conjugated to various biomaterials (e.g., collagen, gelMA) to enable nondestructive, longitudinal measurement of degradation and/or drug delivery from implantable scaffolds. A spectral library of nanoparticle probes (Au, HfO2, Gd2O3) has been developed to leverage the capabilities of spectral CT and function as a radiopharmacy analogous to that used in nuclear imaging. Moreover, photon-counting spectral CT was shown, for the first time, to enable quantitative molecular imaging of multiple spatially coincident contrast agent and tissue compositions.