Fluorine magnetic resonance imaging (19F MRI) is a promising imaging technique for cancer diagnosis because of its excellent soft tissue resolution and deep tissue penetration, as well as the inherent high natural abundance, almost no endogenous interference, quantitative analysis, and wide chemical shift range of the 19F nucleus. In recent years, scientists have synthesized various 19F MRI contrast agents. By further integrating a wide variety of nanomaterials and cutting‐edge construction strategies, magnetically equivalent 19F atoms are super‐loaded and maintain satisfactory relaxation efficiency to obtain high‐intensity 19F MRI signals. In this review, the nuclear magnetic resonance principle underlying 19F MRI is first described. Then, the construction and performance of various fluorinated contrast agents are summarized. Finally, challenges and future prospects regarding the clinical translation of 19F MRI nanoprobes are considered. This review will provide strategic guidance and panoramic expectations for designing new cancer theranostic regimens and realizing their clinical translation.

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Fluorine-19 magnetic resonance imaging (19F MRI) probes have received considerable research interest as imaging contrast agents (CAs), but they remain neglected and underutilized due to the limited fluorine content or poor performance of fluorinated tracers. Here, we present polymeric nanoparticles (NPs) as 19F MRI CAs with a simple synthesis method and promising imaging performance. First, hydrophilic random copolymers were synthesized from oligo(ethylene glycol) methyl ether acrylate and perfluoropolyether methacrylate by reversible addition-fragmentation chain transfer (RAFT) polymerization. The optimal fluorine content, polymer concentration, and cytotoxicity as 19F MRI CAs were investigated in detail. Then, the optimal copolymer was selected as the macromolecular chain transfer agent, and the chain extension was performed with 2-(perfluorooctyl ethyl methacrylate). Subsequently, the NPs with different morphologies, such as ellipsoidal, spherical nanoparticles and vesicles, were prepared in situ by the RAFT-mediated polymerization-induced self-assembly method. In addition, the 19F MRI signal and cytotoxicity studies further confirmed that these polymeric NPs are nontoxic and have great potential as promising 19F MRI CAs for biological applications.

19 F magnetic resonance imaging (MRI)-assisted drug delivery provides the possibility to monitor and track drug transportation details in situ. A series of photo-responsive amphiphilic block copolymers consisting of hydrophilic poly(ethylene glycol) and 19 F-containing hydrophobic segments, poly(2,2,2-trifluoroethyl acrylate) (PTFEA), with different chain lengths were synthesized by reversible addition−fragmentation chain-transfer polymerization. In particular, the photo-sensitive functional group of o-nitrobenzyl oxygen was introduced to control the photolysis behavior of the copolymers under ultraviolet irradiation. With the extension of the hydrophobic chain length, the drug loading capacity and photoresponsivity were both enhanced, while the chain mobility of PTFEA was suppressed, and the 19 F MRI signal was attenuated. When the polymerization degree of PTFEA was about 10, the nanoparticles exhibit detectable 19 F MRI signals and sufficient drug loading capacity (loading efficiency = 10%, cumulative release = 49%). These results offer a promising "smart" theranostic platform for 19 F MRI.