A nephrotoxicity-free, iron-based contrast agent for magnetic resonance imaging of tumors

Xue, Xiangdong; Bo, Ruonan; Qu, Haijing; Jia, Bei; Xiao, Wenwu; Yuan, Ye; Vapniarsky, Natalia; Lindstrom, Aaron; Wu, Hao; Zhang, Dalin; Li, Longmeng; Ricci, Marina; Ma, Zhao; Zhu, Zheng; Lin, Tzu‐Yin; Louie, Angelique Y.; Li, Yuanpei

doi:10.1016/j.biomaterials.2020.120234

Cited by 24 publications

(14 citation statements)

References 68 publications

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“…In addition to magnetic and crystalline properties, the essential properties of iron-oxide nanoparticles must also be considered, such as size, surface charge, and lipophilicity [ 40 ]. Iron is a physiologically ubiquitous element in the mammalian body and is more easily metabolized than the conventionally used gadolinium-based contrast agents [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

Kader

Kaufmann

Mangarova

et al. 2022

Cancers

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Prostate cancer (PCa) is one of the most common cancers in men. For detection and diagnosis of PCa, non-invasive methods, including magnetic resonance imaging (MRI), can reduce the risk potential of surgical intervention. To explore the molecular characteristics of the tumor, we investigated the applicability of ferumoxytol in PCa in a xenograft mouse model in two different tumor volumes, 500 mm3 and 1000 mm3. Macrophages play a key role in tumor progression, and they are able to internalize iron-oxide particles, such as ferumoxytol. When evaluating T2*-weighted sequences on MRI, a significant decrease of signal intensity between pre- and post-contrast images for each tumor volume (n = 14; p < 0.001) was measured. We, furthermore, observed a higher signal loss for a tumor volume of 500 mm3 than for 1000 mm3. These findings were confirmed by histological examinations and laser ablation inductively coupled plasma-mass spectrometry. The 500 mm3 tumors had 1.5% iron content (n = 14; σ = 1.1), while the 1000 mm3 tumors contained only 0.4% iron (n = 14; σ = 0.2). In vivo MRI data demonstrated a correlation with the ex vivo data (R2 = 0.75). The results of elemental analysis by inductively coupled plasma-mass spectrometry correlated strongly with the MRI data (R2 = 0.83) (n = 4). Due to its long retention time in the blood, biodegradability, and low toxicity to patients, ferumoxytol has great potential as a contrast agent for visualization PCa.

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Section: Discussionmentioning

confidence: 99%

Iron Oxide Nanoparticles for Visualization of Prostate Cancer in MRI

Kader

Kaufmann

Mangarova

et al. 2022

Cancers

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“…Currently, most clinical T 1 CAs are gadolinium (Gd) chelates, including Magnevist (Gd-DTPA), Gadavist (Gd-DO3A-Butriol), Dotarem (Gd-DOTA), Eovist (Gd-EOB-DTPA), Omniscan (Gd-DTPA-BMA), and so on [9][10][11][12]. However, the U.S. food and drug administration (FDA) has warned that the Gd chelates tend to cause nephrogenic system fibrosis and cerebral deposition [13][14][15]. In addition, the T 1 imaging capability of the commercial Gd chelates is not strong due to their small longitudinal relaxivity (r 1 , ~ 4 mM −1 s −1 ) [16].…”

Section: Introductionmentioning

confidence: 99%

Biodegradable and biocompatible exceedingly small magnetic iron oxide nanoparticles for T1-weighted magnetic resonance imaging of tumors

Zhou

Liang

et al. 2022

J Nanobiotechnol

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Magnetic resonance imaging (MRI) has been widely using in clinical diagnosis, and contrast agents (CAs) can improve the sensitivity MRI. To overcome the problems of commercial Gd chelates-based T1 CAs, commercial magnetic iron oxide nanoparticles (MIONs)-based T2 CAs, and reported exceedingly small MIONs (ES-MIONs)-based T1 CAs, in this study, a facile co-precipitation method was developed to synthesize biodegradable and biocompatible ES-MIONs with excellent water-dispersibility using poly (aspartic acid) (PASP) as a stabilizer for T1-weighted MRI of tumors. After optimization of the synthesis conditions, the final obtained ES-MION9 with 3.7 nm of diameter has a high r1 value (7.0 ± 0.4 mM−1 s−1) and a low r2/r1 ratio (4.9 ± 0.6) at 3.0 T. The ES-MION9 has excellent water dispersibility because of the excessive –COOH from the stabilizer PASP. The pharmacokinetics and biodistribution of ES-MION9 in vivo demonstrate the better tumor targetability and MRI time window of ES-MION9 than commercial Gd chelates. T1-weighted MR images of aqueous solutions, cells and tumor-bearing mice at 3.0 T or 7.0 T demonstrate that our ES-MION9 has a stronger capability of enhancing the MRI contrast comparing with the commercial Gd chelates. The MTT assay, live/dead staining of cells, and H&E-staining indicate the non-toxicity and biosafety of our ES-MION9. Consequently, the biodegradable and biocompatible ES-MION9 with excellent water-dispersibility is an ideal T1-weighted CAs with promising translational possibility to compete with the commercial Gd chelates.

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“…Actually, due to their extremely small size (below 5 nm), USPIO NPs can cross the kidney filtration system, which allows their rapid excretion in the urine, guaranteeing their easy clearance and favorable biocompatibility in biological applications. 43 Xue et al 44 developed nano-enabled, iron-based T 1 MRI CAs without nephrotoxicity, which produced a significantly high signal-to-noise ratio (SNR) and rapid urine excretion, making them desirable for precisely localizing tumors in vivo . Thus, these T 1-weighted MRI CAs are anticipated to be alternative clinical Gd-based CAs for patients with kidney dysfunction.…”

Section: Basic Principles Of Mri and Common Mri Casmentioning

confidence: 99%