Water-Soluble Chemically Precise Fluorinated Molecular Clusters for Interference-Free Multiplex ¹⁹F MRI in Living Mice.

Abstract

Fluorine-19 magnetic resonance imaging (¹⁹F MRI) is gaining widespread interest from the fields of biomolecule detection, cell tracking, and diagnosis, benefiting from its negligible background, deep tissue penetration, and multispectral capacity. However, a wide range of ¹⁹F MRI probes are in great demand for the development of multispectral ¹⁹F MRI due to the limited number of high-performance ¹⁹F MRI probes. Herein, we report a type of water-soluble molecular ¹⁹F MRI nanoprobe by conjugating fluorine-containing moieties with a polyhedral oligomeric silsesquioxane (POSS) cluster for multispectral color-coded ¹⁹F MRI. These chemically precise fluorinated molecular clusters are of excellent aqueous solubility with relatively high ¹⁹F contents and of single ¹⁹F resonance frequency with suitable longitudinal and transverse relaxation times for high-performance ¹⁹F MRI. We construct three POSS-based molecular nanoprobes with distinct ¹⁹F chemical shifts at -71.91, -123.23, and -60.18 ppm and achieve interference-free multispectral color-coded ¹⁹F MRI of labeled cells <i>in vitro</i> and <i>in vivo</i>. Moreover, <i>in vivo</i> ¹⁹F MRI reveals that these molecular nanoprobes could selectively accumulate in tumors and undergo rapid renal clearance afterward, illustrating their favorable <i>in vivo</i> behavior for biomedical applications. This study provides an efficient strategy to expand the ¹⁹F probe libraries for multispectral ¹⁹F MRI in biomedical research.