¹⁹F Barcoding Enables Multiplex Detection of Biomarkers Associated with Organ Injury and Cancer

Abstract

Simultaneous detection of multiple biomarkers in complex environments is critical for the in‐depth exploration of different biological processes, which is challenging for many current analytical methods due to various limitations. Herein, we report a strategy of 19F barcoding which takes the advantages of 19F's high magnetic resonance (MR) sensitivity, prompt signal response to environmental changes, negligible biological background, quantitative signal output, and multiplex capacity. A set of 19F‐barcoded sensors responding to different biomarkers involved in organ injury and cancer are designed, synthesized, and characterized. With these sensors, we accomplish concurrent assessment of different biomarkers in the samples collected from the mice with drug‐induced liver/kidney injury or tumor, illustrating the feasibility of this approach for multiplexed detection of different biomarkers in complex environments during various biological processes.

Small Molecule Probes for 19F Magnetic Resonance Imaging

“…Despite substantial achievement, most of the studies on this type of probe focus on a single target, which does not fully release their potential and take advantage of the multiplexity of 19 F MR signals. Recently, we developed a set of this type of probe based on fluoroaniline and fluorophenol, which could detect several bioactive molecules including leucine aminopeptidase (LAP), aminopeptidase N (AAP), γ-glutamyl transpeptidase (GGT), monoamine oxidases (MAO), and β-N-acetylglucosamines (NAG) (Figure c) . The 19 F chemical shifts of these probes and their sensing products are significantly different from each other, which allows sensitive and quantitative multiplex assessment of these biomarkers without mutual interferences in complex biological environments, demonstrating the promising potential of this type of probe for concurrent detection of multiple targets during various biological processes.…”

Glycan Metabolic Fluorine Labeling for In Vivo Visualization of Tumor Cells and In Situ Assessment of Glycosylation Variations

“…Among other nuclei suitable for MRI, 19 F draws the attention of the research community because of its high MR sensitivity (comparable to that of 1 H), 100 % natural abundance, and negligible biological background [24–31] . Besides, the wide range of 19 F chemical shifts (>350 ppm) and the diversity of biocompatible fluorine‐containing agents permit multi‐spectral color‐coded 19 F MRI that is capable of tracing multiple targets [32–36] . In addition, in vivo quantitative analysis, which is difficult for many imaging techniques, is enabled by the quantitative nature of MR and the low biological background of 19 F [37–38] .…”

“…[24][25][26][27][28][29][30][31] Besides, the wide range of 19 F chemical shifts (> 350 ppm) and the diversity of biocompatible fluorine-containing agents permit multi-spectral color-coded 19 F MRI that is capable of tracing multiple targets. [32][33][34][35][36] In addition, in vivo quantitative analysis, which is difficult for many imaging techniques, is enabled by the quantitative nature of MR and the low biological background of 19 F. [37][38] Therefore, 19 F MRI has been one of the most promising imaging techniques for tracking in vivo biological targets. [20,[39][40][41][42][43] Recently, we reported a strategy, bioorthogonal metabolic fluorine labeling (BOMFLA), for in vivo visualization of cancer cells, which utilized tetraacetylated N-azidoacetylmannosamine (Ac 4 ManAz) for incorporating azido groups to the surface glycans of cancer cells and subsequent SPAAC to introduce 19 F-containing agents for 19 F MRI.…”

Fe(II)-Targeted PET/19F MRI Dual-Modal Molecular Imaging Probe for Early Evaluation of Anticancer Drug-Induced Acute Kidney Injury

“…Of note, there is negligible endogenous 19 F in the body, which makes 19 F MRI a promising complementary modality for conventional 1 H MRI . Currently, a variety of fluorinated molecules and nanoparticles have been developed as 19 F MRI contrast agents. − Among them, fluoropolymers have gained great momentum, owing to their structure flexibility, ease of functionalization, and high fluorine contents. However, the inherent hydrophobicity of the fluorine atoms causes extensive aggregation of fluorinated segments, which compromises imaging sensitivity.…”