JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 7.3
Weiyuan Xu,Xinjian Ye,Min Wu,Xin Jiang,Lik Hang Hugo TSE,Yanjuan Gu,Kun Shu,Liuhui Xu,Yong Jian,Gengshen Mo,Jiao Xu,Yinghui Ding,Ruonan Gao,Jianliang Shen,Fangfu Ye,Zhihan Yan,Lixiong Dai
The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.
研究领域:
医学影像学
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分子生物学
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化学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Ting Zhou,Yanzhi Dong,Xiaoyi Wang,Ruxia Liu,Ran Cheng,Jinbin Pan,Xuejun Zhang,Shao-Kai Sun
Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T 1 relaxivity (12.52 m m −1 s −1 ), a small hydrodynamic size (6.43 nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.
研究领域:
医学影像学
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生物材料学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2024
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IF 4.5
Dinghu Weng,Rong Guo,Changling Dong,Yuan Luo,Dasheng Qiu,Liying Xu,Guobin Xu
The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM–1 s–1 and 5.323 mM–1 s–1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.
研究领域:
医学成像
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肿瘤学
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2019
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IF 13.903
Qinjie Weng,Xi Hu,Jiahuan Zheng,Fan Xia,Nan Wang,Hongwei Liao,Ying Liu,Dokyoon Kim,Jianan Liu,Fangyuan Li,Qiaojun He,Bo Yang,Chunying Chen,Taeghwan Hyeon,Daishun Ling
Gadolinium-based contrast agents (GBCAs) are widely used for T1-weighted magnetic resonance imaging (MRI) in clinic diagnosis. However, a major drawback of GBCAs is that they can increase the toxicological risk of nephrogenic systemic fibrosis (NSF) in patients with advanced renal dysfunction. Hence, safer alternatives to GBCAs are currently in demand, especially for patients with renal diseases. Here we investigated the potential of polyethylene glycol (PEG)-stabilized iron oxide nanoclusters (IONCs) as biocompatible T1MRI contrast agents and systematically evaluated their NSF-related risk in rats with renal failure. We profiled the distribution, excretion, histopathological alterations, and fibrotic gene expressions after administration of IONCs and GBCAs. Our results showed that, compared with GBCAs, IONCs exhibited dramatically improved biosafety and a much lower risk of causing NSF, suggesting the feasibility of substituting GBCAs with IONCs in clinical MRI diagnosis of patients with renal diseases.
研究领域:
医学影像
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纳米技术
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药理学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）