TY - JOUR
T1 - MRI Contrasting Agent Based on Mn-MOF-74 Nanoparticles with Coordinatively Unsaturated Sites
AU - Iki, Nobuhiko
AU - Nakane, Ryuta
AU - Masuya-Suzuki, Atsuko
AU - Ozawa, Yoshikazu
AU - Maruoka, Takako
AU - Iiyama, Megumi
AU - Sumiyoshi, Akira
AU - Aoki, Ichio
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Challenging Research (Exploratory) JP18K19087 entitled “Exploration of Science for Designing High Performance MRI Contrast Agents –A New Approach Using Coordinatively Unsaturated Coordination Polymers as a Substrate” in FY 2018–2020 []. This research was also supported by Kakenhi (#21H04966, 21KK0201, 17KK0102) and the MRI devices were partly supported by the Project for promoting public utilization of advanced research infrastructure (JPMXS0450400422, JST/MEXT).
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to World Molecular Imaging Society.
PY - 2023
Y1 - 2023
N2 - Purpose: The development of magnetic resonance imaging (MRI) contrasting agents (CAs) that are safer and have a higher relaxivity than Gd(III)-based agents is a significant research topic. Herein, we propose the use of a Mn-based metal organic framework (MOF), Mn-MOF-74, characterized by a safe paramagnetic center, a coordinatively unsaturated site (CUS) for aquation, and a long rotational correlation time, endowing high relaxivity. Furthermore, biocompatibility and delivery to the tumor are generally expected for MOFs that are obtainable in the nanometer size range. Procedure: Drop-wise mixing of 2,5-dihydroxyterephthalic acid (DHTP) and Mn(II) acetate yielded Mn-MOF-74 with a diameter of < 150 nm, which was then modified with 1–fivefold higher amounts of poly(ethylene glycol) (M.W. = 5000) to afford MOFs stably dispersed in water for at least 24 h. Results: The longitudinal and transverse relaxivity of the PEG-modified MOF was in the range of r1 = 8.08–13.5 and r2 = 32.7–46.8 mM–1 s–1, respectively (1.0 T, 23.7–23.9 °C), being larger than those of typical Gd(III)- and Mn(II)-based CAs of single-nuclear metal complexes. The in vivo imaging of a tumor-bearing mouse clearly showed that the tumor could be readily recognized due to signal enhancement (117%) in T1-weighted images, whereas other tissues showed small signal changes. Conclusions: These results suggest that PEG-Mn-MOF-74 can be passively delivered to tumors and can act as a high-relaxivity T1 agent.
AB - Purpose: The development of magnetic resonance imaging (MRI) contrasting agents (CAs) that are safer and have a higher relaxivity than Gd(III)-based agents is a significant research topic. Herein, we propose the use of a Mn-based metal organic framework (MOF), Mn-MOF-74, characterized by a safe paramagnetic center, a coordinatively unsaturated site (CUS) for aquation, and a long rotational correlation time, endowing high relaxivity. Furthermore, biocompatibility and delivery to the tumor are generally expected for MOFs that are obtainable in the nanometer size range. Procedure: Drop-wise mixing of 2,5-dihydroxyterephthalic acid (DHTP) and Mn(II) acetate yielded Mn-MOF-74 with a diameter of < 150 nm, which was then modified with 1–fivefold higher amounts of poly(ethylene glycol) (M.W. = 5000) to afford MOFs stably dispersed in water for at least 24 h. Results: The longitudinal and transverse relaxivity of the PEG-modified MOF was in the range of r1 = 8.08–13.5 and r2 = 32.7–46.8 mM–1 s–1, respectively (1.0 T, 23.7–23.9 °C), being larger than those of typical Gd(III)- and Mn(II)-based CAs of single-nuclear metal complexes. The in vivo imaging of a tumor-bearing mouse clearly showed that the tumor could be readily recognized due to signal enhancement (117%) in T1-weighted images, whereas other tissues showed small signal changes. Conclusions: These results suggest that PEG-Mn-MOF-74 can be passively delivered to tumors and can act as a high-relaxivity T1 agent.
KW - Contrast agents
KW - Metal organic framework
KW - Mn(II)
KW - MRI
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U2 - 10.1007/s11307-023-01801-0
DO - 10.1007/s11307-023-01801-0
M3 - Article
AN - SCOPUS:85146391742
SN - 1536-1632
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
ER -
