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19F MRI
BIOMACROMOLECULES · 2024 · IF 5.5

Hyperbranched Polymeric 19F MRI Contrast Agents with Long T2 Relaxation Time Based on β-Cyclodextrin and Phosphorycholine

Jialei Han,Ziwei Duan,Changjiang Liu,Yadong Liu,Xinyu Zhao,Bo Wang,Shuaishuai Cao,Dalin Wu

19F magnetic resonance imaging (19F MRI) is gaining attention as an emerging diagnostic technology. Effective 19F MRI contrast agents (CAs) for in vivo applications require a long transverse (or spin–spin) relaxation time (T2), short longitudinal (or spin–lattice) relaxation time (T1), high fluorine content, and excellent biocompatibility. Here, we present a novel hyperbranched polymeric 19F MRI CA based on β-cyclodextrin and phosphorylcholine. The influence of the branching degree and fluorine content on T2 was thoroughly investigated. Results demonstrated a maximum fluorine content of 11.85% and a T2 of 612 ms. This hyperbranched polymeric 19F MRI CA exhibited both great biocompatibility against cells and organs of mice and high-performance imaging capabilities both in vitro and in vivo. The research provides positive insights into the synthesis strategies, topological design, and selection of fluorine tags for 19F MRI CAs.

研究领域: 医学影像学 · 材料科学 · 生物医学工程
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RSC Advances · 2023 ·Vol. 13 ·期 32 ·22335-22345 · IF 3.9

Fluorinated hydrogel nanoparticles with regulable fluorine contents and T2 relaxation times as 19F MRI contrast agents

Ziwei Duan,Changjiang Liu,Junjie Tang,Ruling Zhang,Danfeng Peng,Ruitao Lu,Zong Cao,Dalin Wu

Medical imaging contrast agents that are able to provide detailed biological information have attracted increasing attention. Among the new emerging imaging contrast agents, 19F magnetic resonance imaging contrast agents (19F MRI CAs) are extremely promising for their weak background disturbing signal from the body. However, to prepare 19F MRI CAs with a long T2 relaxation time and excellent biocompatibility in a simple and highly effective strategy is still a challenge. Herein, we report a new type of 19F MRI hydrogel nanocontrast agents (19F MRI HNCAs) synthesized by a surfactant-free emulsion polymerization with commercial fluorinated monomers. The T2 relaxation time of 19F MRI HNCA-1 was found to be 25–40 ms, guaranteeing its good imaging ability in vitro. In addition, according to an investigation into the relationship between the fluorine content and 19F MRI signal intensity, the 19F MRI signal intensity was not only determined by the fluorine content in 19F MRI HNCAs but also by the hydration microenvironment around the fluorine atoms. Moreover, 19F MRI HNCAs demonstrated excellent biocompatibility and imaging capability inside cells. The primary exploration demonstrated that 19F MRI HNCAs as a new type of 19F MRI contrast agent hold potential for imaging lesion sites and tracking cells in vivo by 19F MRI technology.

CAS / MDL: 298-93-1
研究领域: 医学成像 · 材料科学 · 纳米技术 · 生物医学工程
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Advanced Science · 2024 · IF 14.3

19F MRI/CEUS Dual Imaging-Guided Sonodynamic Therapy Enhances Immune Checkpoint Blockade in Triple-Negative Breast Cancer

Qiu Chen,Hong Xiao,Lijun Hu,Yongquan Huang,Zhong Cao,Xintao Shuai,Zhongzhen Su

Treatment of highly aggressive triple-negative breast cancer (TNBC) in the clinic is challenging. Here, a liposome nanodrug (LP@PFH@HMME) integrating imaging agents and therapeutic agents for bimodal imaging-guided sonodynamic therapy (SDT) is developed, which boosted immunogenicity to enable potent immunotherapy via immune checkpoint blockade (ICB) in TNBC. In the acidic tumor microenvironment (TME), LP@PFH@HMME undergoes “nano-to-micro” transformation due to a pH-responsive lipid fusion, which makes droplets much more sensitive to ultrasound (US) in contrast-enhanced ultrasound (CEUS) and SDT studies. The nanodrug demonstrates robust bimodal imaging ability through fluorine-19 magnetic resonance imaging ( 19 F MRI) and CEUS bimodal imaging, and it exhibits excellent solubility in aqueous solution with relatively high 19 F content and desirable long transverse relaxation time (T 2 = 1.072 s), making it suitable for high-performance 19 F MRI, in addition to effective accumulation of nanodrugs after tail vein injection. Thus, 19 F MRI/CEUS dual imaging is achievable to show adequate time points for US irradiation of tumor sites to induce highly effective SDT, which produces abundant reactive oxygen species (ROS) triggering immunogenic cell death (ICD) to assist ICB-based immunotherapy. The combination treatment design of sonodynamic therapy with immunotherapy effectively inhibited TNBC growth and recurrence, highlighting the promise of multifunctional nanodrugs in treating TNBC.

CAS / MDL: 816-94-4
研究领域: 医学影像 · 癌症治疗 · 纳米技术 · 免疫疗法
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BIOMACROMOLECULES · 2023 · IF 6.2

Photo-Responsive Self-Assembled Polymeric Nanoparticle Probes for 19F MRI Theranostics

Chenlong Li,Huimin Zhou,Jingjiang Sun,Deshuo Wang,Jun Chang,Qingfu Wang,Yanan Li,Wei Zhao

19F 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 19F-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 19F MRI signal was attenuated. When the polymerization degree of PTFEA was about 10, the nanoparticles exhibit detectable 19F MRI signals and sufficient drug loading capacity (loading efficiency = 10%, cumulative release = 49%). These results offer a promising “smart” theranostic platform for 19F MRI.

研究领域: 材料科学 · 聚合物化学 · 分子影像 · 纳米医学
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

19F MRI-fluorescence imaging dual-modal cell tracking with partially fluorinated nanoemulsions

Tang Ting,Zhu Qiang,Liu Shuang,Dai Hailong,Li Yu,Tang Caihong,Chen Kexin,Jiang Mou,Zhu Lijun,Zhou Xin,Chen ShiZhen,Zheng Zitong,Jiang Zhong-Xing

As a noninvasive “hot-spot” imaging technology, fluorine-19 magnetic resonance imaging (19F MRI) has been extensively used in cell tracking. However, the peculiar physicochemical properties of perfluorocarbons (PFCs), the most commonly used 19F MRI agents, sometimes cause low sensitivity, poor cell uptake, and misleading results. In this study, a partially fluorinated agent, perfluoro-tert-butyl benzyl ether, was used to formulate a 19F MRI-fluorescence imaging (FLI) dual-modal nanoemulsion for cell tracking. Compared with PFCs, the partially fluorinated agent showed considerably improved physicochemical properties, such as lower density, shorter longitudinal relaxation times, and higher solubility to fluorophores, while maintaining high 19F MRI sensitivity. After being formulated into stable, monodisperse, and paramagnetic Fe3+-promoted nanoemulsions, the partially fluorinated agent was used in 19F MRI-FLI dual imaging tracking of lung cancer A549 cells and macrophages in an inflammation mouse model.

CAS / MDL: 8001-22-7
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ANALYTICAL CHEMISTRY · 2023 · IF 7.4

High-Sensitivity, Low-Field 19F-MRI Approach Using High Manganese Ferrite Concentrations

Yupeng Cao,Xiaohan Zhou,Xiaoli Liu,Mei Yang,Wentao Liu,Dong Han

Fluorine-19 (19F) MRI (19F-MRI) is a promising method for quantifying biomedical research and clinical applications without background interference. Nevertheless, dependency on high-field MRI systems limits the applicability of 19F-MRI. Low-field MRI systems are more common than high-field MRI systems. Hence, developing 19F-MRI at low-field MRI devices can promote the 19F-MRI translation in medical diagnosis. The detection sensitivity of fluorine agents is critical in 19F-MRI. Reduction of the 19F spin-lattice relaxation time (T1) enables an improved detection sensitivity while requiring ultrashort echo time (UTE) imaging methods to reduce the negative spin–spin relaxation (T2) decay effect. However, conventional UTE sequences require hardware with high performance. Herein, we introduce the k-space scaling imaging (KSSI) MRI sequence that accomplishes sampling k-space with variable scales to implement hardware-friendly UTE 19F-MRI compatible with low-field MRI systems. We implemented experiments with swine bone, a perfluorooctyl bromide (PFOB) phantom, and one tumor-bearing mouse on two self-customized low-field MRI systems. The swine bone imaging validated the ultrashort TE of KSSI. Under high concentrations of manganese ferrite, a high signal-to-noise ratio was shown in the imaging of a fluorine atom concentration of 658 mM, which indicated high-sensitivity detection of KSSI. Moreover, the KSSI sequence exhibited a 7.1 times signal-to-noise ratio of spin echo sequence on the PFOB phantom imaging with a fluorine atom concentration of 3.29 M. Additionally, the various concentrations of the PFOB phantom imaging revealed quantifiable capacity. Finally, the 1H/19F imaging was implemented with KSSI on one tumor-bearing mouse. This method provides the potential for clinical translation of fluorine probes at low-field MRI systems.

CAS / MDL: 423-55-2 110-54-3
研究领域: 医学影像 · 生物医学工程
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Superhydrophilic Fluorinated Polymer Probe for Zero-Background 19F MRI with Adaptable Targeting Ability

Chang Guo,Xiaoyao Xiong,Xinxing Zhao,Yumin Li,Sijia Li,Suying Xu,Tony D. James,Leyu Wang

19F magnetic resonance imaging (19F MRI), with zero background, high tissue penetration depth, excellent spatial resolution, and nonradioactive features, has attracted considerable attention but faces tough challenges due to the shortage of sensitive and selective targetable probes. Herein, we report a biocompatible and highly sensitive 19F MRI probe with an adaptable tumor-targeting ability. The fluorine-grafted polymer (PIBMA-FSON) probes were rich with sulfoxide and carboxy groups, containing a high fluorine content (∼17 wt %). The probes exhibit superhydrophilicity, strong 19F MRI signals (enhancement of ∼95-fold), long transverse relaxation time (T2, 422 ms), and excellent 19F MRI capability. Conjugation using a targeting peptide (Arg-Gly-Asp, RGD) afforded ultrasmall soft polymer probes (PIBMA-FSON-RGD) with superhydrophilicity and tumor-targeting ability suitable for the 19F MRI of orthotopic bladder cancer. Amidification of 5% of the carboxylate units with oleylamine resulted in PIBMAOAm-FSON nanoprobes (NPs) via self-assembly, displaying different targeting toward subcutaneous tumors. Further grafting with near-infrared (NIR) dyes renders the probe suitable for NIR-fluorescence and 19F MRI dual-modality imaging. This study provides a suitable approach for designing highly sensitive and zero-background 19F MRI probes with a tunable tumor-targeting ability.

CAS / MDL: 3326-34-9
研究领域: 医学影像学 · 生物材料学 · 分子影像学
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ANALYTICAL CHEMISTRY · 2022 · IF 8.008

Acid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo–Chemodynamic Therapy

Ruijuan Zhang,Qian Ma,Gaofei Hu,Leyu Wang

The real-time tracking and efficacy evaluation of therapeutic nanoplatforms especially in deep-tissues is of great importance but faces challenges. Meanwhile, chemodynamic therapy (CDT), relying on Fenton reaction by converting H2O2 into toxic hydroxyl radicals (•OH), has drawn wide interests in the fabrication of nanozymes for tumor therapy, while endogenous H2O2 is usually insufficient for effective CDT. Here, we report the pH-responsive multifunctional nanoplatforms consisting of copper peroxide (CP) nanoparticles, paclitaxel (PTX) and perfluoro-15-crown-5-ether (PFCE), for 19F magnetic resonance imaging guided and enhanced chemo–chemodynamic synergetic therapy with self-supplied H2O2 stemmed from the decomposition of CP nanoparticles under acid conditions in tumor. The decomposition of CP nanoparticles further promotes the release of PTX for enhanced chemotherapy. Both in vitro and in vivo results indicate that the efficient generation of •OH and drug release effectively inhibits tumor growth. Furthermore, 19F MRI signal can clearly track the fate of nanoplatforms in tumor and guide tumor treatment. This work provides a promising strategy for the rational design and construction of multifunctional nanoplatforms for imaging-guided synergistic therapy of deep seated tumor.

研究领域: 肿瘤学 · 生物医学工程 · 影像医学
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ACS Applied Materials & Interfaces · 2026 ·Vol. 18 ·期 29 ·39757-39770 · IF 7.8

Biomineralization-Derived Gadolinium Nanoparticles for Dual-Modal 1H/19F MRI-Guided Photodynamic Tumor Therapy

Si Tingzhao,Li Tuohuan,Xiao Wenqing,Wang Kai,Pan Yue,Zhu Yuyu,Cao Zhong

The integration of conventional 1 H MRI with heteronuclear 19 F MRI enables the concurrent acquisition of complementary anatomical and molecular imaging information using a single instrument. Here, we report a T 1 -T 2 dual-modal MRI platform based on gadolinium-albumin (Gd-BSA) nanostructures synthesized through a biomimetic mineralization strategy. To endow multifunctionality, perfluoropentaphenyl-15-crown-5 ether (PFCE) and the photosensitizer IR780 were coencapsulated, yielding the theranostic probe IR780@PFCE@Gd-BSA (IPGB). IPGB exhibited strong 19 F MRI signals and T 1 -T 2 contrast enhancement on clinical and preclinical MRI systems (1.5, 3.0, and 9.4 T), confirming its potential for 1 H/ 19 F multimodal imaging. Beyond imaging, IPGB exhibited superior photodynamic therapy (PDT) efficacy compared with free IR780. In vivo , IPGB achieved passive tumor accumulation with prolonged retention, enabled high-resolution multimodal MRI, and significantly suppressed breast tumor growth after PDT. Collectively, these results highlight IPGB as a viable multifunctional nanoplatform for cancer diagnosis, real-time multimodal imaging, and image-guided therapy.

CAS / MDL: 13450-84-5 5471-63-6
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

Self-immolative fluorinated nanotheranostics amplifying 19F MRI signals for tumor-specific imaging and photodynamic therapy

Ruling Zhang,Kai Wang,Wenqing Xiao,Dalin Wu,Zhong Cao

Fluorine-19 magnetic resonance imaging ( 19 F MRI) offers distinct advantages, including background-free signal detection, quantitative analysis, and deep tissue penetration. However, its application is currently limited by challenges associated with existing 19 F MRI contrast agents, such as short transverse relaxation times (T 2 ), limited imaging sensitivity, and suboptimal biocompatibility. To overcome these limitations, a glutathione (GSH)-responsive triblock copolymer (PB7), featuring self-immolative characteristics, has been developed. In aqueous solution, PB7 can spontaneously self-assemble into a 19 F MRI contrast agent (SPTF), which exhibits a long T 2 relaxation time and GSH-responsive T 2 prolongation. Notably, during the self-assembly process of PB7, the photosensitizer Chlorin e6 (Ce6) can be encapsulated inside of the hydrophobic domain of SPTF, resulting in the formation of a multifunctional nanotheranostic agent (Ce6@SPTF). Ce6@SPTF is able to undergo structural disintegration in response to elevated GSH levels at the tumor site, leading to the dissociation of fluorinated segments and a marked amplification of the 19 F MRI signal. Concurrently, the controlled release of Ce6 generates high levels of reactive oxygen species (ROS) under laser irradiation, enabling effective in vivo ablation of breast tumors. This study presents a promising strategy to effectively combine 19 F MRI with therapeutic interventions.

研究领域: 医学影像 · 纳米医学 · 肿瘤学 · 磁共振成像 · 光动力治疗 · 生物医学工程
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