Fast detection of liver fibrosis with collagen-binding single-nanometer iron oxide nanoparticles via <i>T</i> <sub>1</sub> -weighted MRI
Juanye Zhang, Yingying Ning, Hua Xing Zhu, Nicholas J. Rotile, Wei He, H.V.K. Diyabalanage, Eric C. Hansen, Iris Y. Zhou, Stephen C. Barrett, Mozhdeh Sojoodi, Kenneth K. Tanabe, Valérie Humblet, Alan Jasanoff, Peter Caravan, Moungi G. Bawendi
Abstract
SNIO–CBP, a single-nanometer iron oxide (SNIO) nanoparticle functionalized with a type I collagen-binding peptide (CBP), was developed as a T 1 -weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO–CBP exhibits 6.7-fold higher relaxivity compared to a molecular gadolinium-based collagen-binding contrast agent CM-101 on a per CBP basis at 4.7 T. Unlike most iron oxide nanoparticles, SNIO–CBP exhibits fast elimination from the bloodstream with a 5.7 min half-life, high renal clearance, and low, transient liver enhancement in healthy mice. We show that a dose of SNIO–CBP that is 2.5-fold lower than that for CM-101 has comparable imaging efficacy in rapid (within 15 min following intravenous injection) detection of hepatotoxin-induced liver fibrosis using T 1 -weighted MRI in a carbon tetrachloride–induced mouse liver injury model. We further demonstrate the applicability of SNIO–CBP in detecting liver fibrosis in choline-deficient L -amino acid-defined high-fat diet mouse model of nonalcoholic steatohepatitis. These results provide a platform with potential for the development of high relaxivity, gadolinium-free molecular MRI probes for characterizing chronic liver disease.