Activatable Multiplexed ¹⁹F Magnetic Resonance Imaging Visualizes Reactive Oxygen and Nitrogen Species in Drug-Induced Acute Kidney Injury

Abstract

In vivo levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are critical to many physiological and pathological processes. Because of the distinct differences in their biological generation and effects, simultaneously visualizing both of them could help deepen our insights into the mechanistic details of these processes. However, real-time and deep-tissue imaging and differentiation of ROS-and RNS-related molecular events in living subjects still remain a challenge. Here, we report the development of two activatable 19 F magnetic resonance imaging (MRI) molecular probes with different 19 F chemical shifts and specific responsive behaviors for simultaneous in vivo detection and deep-tissue imaging of O 2•− and ONOO − . These probes are capable of real-time visualization and differentiation of O 2•− and ONOO − in living mice with drug-induced acute kidney injury by interference-free multiplexed hot-spot 19 F MRI, illustrating the potential of this technique for background-free real-time imaging of diverse biological processes, accurate diagnosis of various diseases in deep tissues, and rapid toxicity evaluation of assorted drugs.

Bio-orthogonal Metabolic Fluorine Labeling Enables Deep-Tissue Visualization of Tumor Cells In Vivo by 19F Magnetic Resonance Imaging

“…Moreover, in theory, BOMFLA could be used to label engineered cells in vitro, such as chimeric antigen receptor T cells, allowing for their in vivo tracking via 19 F MRI, which is critical for the investigations of cell behaviors in vivo and the assessments of cell-based therapies. With the multiplexity of 19 F MRI, ,− simultaneous in vivo monitoring of multiple types of engineered cells could even be accomplished.…”

Exploiting the Fluxionality of Lanthanide Complexes in the Design of Paramagnetic Fluorine Probes

“…Naturally occurring fluorine is 100% the 19 F isotope, which has a spin of 1/2 and has the highest receptivity of heteronuclei at 83% that of 1 H. Nonetheless, this high receptivity is not sufficient to garner the necessary sensitivity for many applications. Thus, in vivo translation of 19 F MRI remains challenging, though successful imaging of small animals has been achieved with highly fluorinated nanoparticles or liposomes, ,, perfluoropolyethers, , and small organic molecules. , Following the success of ParaCEST (paramagnetic chemical exchange saturation transfer) agents, we and others ,− have attempted to use the same approach to increase the sensitivity of fluorinated probes on a per 19 F basis by decreasing their longitudinal relaxation times ( T 1 ) via the incorporation of paramagnetic metals. Decreasing the T 1 of 19 F enables the acquisition of more scans per given amount of time, a critical restriction for in vivo imaging, which is time-constrained.…”

An Activatable 19F MRI Molecular Probe for Sensing and Imaging of Norepinephrine

“…[30][31][32][33][34][35][36] Therefore, 19 F MRI is gaining momentum in the field of sensing and imaging low concentration bioactive species. [37][38][39][40][41][42][43][44][45][46][47] In light of these considerations, we envision that detecting NE with 19 F MRI might offer a potential means to circumvent the obstacles encountered by fluorescent approaches. We design a norepinephrine-responsive 19 F MRI probe (NRFP) by linking a Gd chelate (Gd-DOTA) to a fluorine-containing small molecule 3,5-bis(trifluoromethyl)benzenethiol (BTFBT) via an aromatic thiocarbonate linkage, which is specifically responsive to NE.…”