Molecular Imaging
·
2016
·
IF 2.216
Pu Zhang,Zhide Guo,Deliang Zhang,Chang Liu,Guibing Chen,Rongqiang Zhuang,Manli Song,Hua Wu,Xianzhong Zhang
The aim of this study is to develop a copolymer-based single-photon emission computed tomography/magnetic resonance (SPECT/MR) dual-modality imaging agent that can be labeled with both technetium-99m (99mTc) and gadolinium (Gd) and target asialoglycoprotein receptor (ASGPR) via galactose. Monomers of N-p-vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono) nicotinate (VNI) for labeling of 99mTc, 5,8-bis(carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid (V2DTPA) for labeling of Gd, and vinylbenzyl-O-β-d-galactopyranosyl-d-gluconamide (VLA) for targeting ASGPR were synthesized, respectively. Then the copolymer P(VLA-co-VNI-co-V2DTPA) (pVLND2) was synthesized and characterized by gel permeation chromatography, dynamic light scattering, and high-performance liquid chromatography analysis. After labeling with 99mTc and Gd simultaneously, the radiochemical purity, toxicity, relaxivity (r1), and in vivo SPECT/MR imaging in mice were evaluated. Single-photon emission computed tomography/magnetic resonance imaging and biodistribution results showed that pVLND2 could target ASGPR well. The significantly improved signal to noise ratio was observed in mice liver during MR imaging. All the results suggest that this novel kind of copolymer has the potential to be further developed as a functional SPECT/MR imaging agent.
研究领域:
医学影像学
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分子生物学
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DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
·
2025
·
IF 6.1
Shaowen Yang,Chengwen Zheng,Sixuan Cheng,Li Wen,Pinghui Li,Jianbo Li,Xiaoli Lan,Dawei Jiang
Aptamers are single-stranded oligonucleotides with specific spatial structures. They have been widely used in preclinical studies because of their high affinity and specificity for various biological targets. AS1411, an aptamer targeting the nucleolin overexpressed on the cancer cell membrane, is one of the most promising and extensively studied aptamers. However, extremely low bioavailability due to rapid renal excretion remains a great obstacle for aptamers’ clinical translation. Human serum albumin (HSA), with long blood circulation and excellent biocompatibility, has been an attractive vehicle for extending drugs’ blood half-life in the clinic. This work investigated the effect of an albumin-conjugated strategy in improving aptamers’ tumor targeting in vivo for the first time by taking AS1411 as an example. HSA-AS1411 was synthesized via the maleimide-sulfhydryl reaction. The excellent serum stability and maintained target affinity of HSA-AS1411 were demonstrated in vitro . The pharmacokinetic analysis and tumor SPECT imaging studies revealed that HSA-AS1411 had over 14 times longer circulation half-life and superior tumor uptake than those of AS1411. The immunofluorescence staining of tumor tissues further indicated the improved tumor retention of AS1411 as a result of prolonged blood circulation. Therefore, the HSA-conjugated strategy has a promising prospect in improving aptamers’ tumor targeting for clinical applications.
研究领域:
药理学
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分子生物学
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肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-15
·
IF 10.6
Chen Can,Huang Baoxing,Zhang Ruru,Sun Chaoping,Chen Lei,Ge Jianxian,Zhou Dandan,Li Yueping,Wu Shuwang,Qian Zhiyuan,Zeng Jianfeng,Gao Mingyuan
Background The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. Results In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e. , anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe 3 O 4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe 3 O 4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe 3 O 4 nanoparticle coated with zwitterionic ligands, i.e. , Fe 3 O 4 @DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99m Tc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe 3 O 4 @DMSA was evaluated both in vitro and in vivo through safety assessment experiments. Conclusions We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis. Graphical Abstract
研究领域:
医学影像学
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纳米医学
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生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
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2010
·Vol. 15
·期 4
·591-599
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IF 3.415
Zhu Hua,Huang Liliang,Zhang Yuanqing,Xu Xiaoping,Sun Yanhong,Shen Yu-Mei
To develop technetium- and rhenium-labeled nonsteroidal estrogen imaging agents for estrogen receptor (ER) positive breast tumors, two groups of rhenium and technetium cyclofenil derivatives were synthesized and characterized. The binding affinities of the rhenium complexes for ERs were determined. The tricarbonyl rhenium complex showed the highest binding affinity for ERs (81.2 for ERβ, 16.5 for ERα). Tricarbonyl technetium cyclofenil complexes were obtained in high radiochemical purity and radiochemical yields. The results of studies of their octanol/water partition and in vitro stability are presented. These results demonstrate that these radiolabeled cyclofenil derivatives may be considered as potential breast cancer imaging agents.
研究领域:
医学影像学
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药物化学
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肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
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2023
·Vol. 332
·期 4
·1237-1244
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IF 1.6
Xi Wenke,Zhang Ge,Xue Jingquan,Li Juan,Liu Yu,Wang Jianjun,Yang Wenjiang
Multimodal imaging has become a trend in the development of molecular imaging. For SPECT/MRI dual-modality imaging, we developed a SPECT/MRI dual-modality probe based on superparamagnetic iron oxide nanoparticles. RGDyk peptide and DTPA chelator were used to realize the functionalization of nanoparticles. Both SPECT imaging and T2-weighted MR imaging in vivo on 4T1 tumor-bearing mice showed targeting of the probe, demonstrating the potential of the SPECT/MRI dual-modality probe as a tool for tumor evaluation and diagnosis.
研究领域:
医学影像学
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分子生物学
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纳米医学
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产品关联
DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Zuojie Li,Xiaojiang Duan,Peiwen Han,Guangxing Yin,Yuhao Jiang,Qing Ruan,Junbo Zhang
The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment of prostate cancer (PCa). This study aimed to improve the absolute tumor uptake and tumor-to-background ratios (TBRs) of this novel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys (EuK), that specifically bind to PSMA. We successfully synthesized four radioligands and prepared a total of 12 stable radiotracers by coordinating 99mTc with various coligands. [99mTc]Tc-EUKD-EDDA showed the best pharmacokinetic properties both in vitro and in vivo. It effectively increased the absolute uptake in tumors and resulted in good tumor retention. Rapid clearance in nontarget organs resulted in high TBRs. High-contrast SPECT/CT images were obtained within 2–6 h after injection, suggesting that [99mTc]Tc-EUKD-EDDA has great application potential in time-lapse imaging of PCa, which is important for improving the diagnostic accuracy of PCa in clinical practice.
研究领域:
医学影像学
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核医学
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肿瘤学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Haoran Xu,Yongjia Tang,Yue Zhao,Fang Wang,Xin Gao,Dawei Deng,Yueqing Gu
The glypican-3 (GPC3) receptor is a membrane protein that is highly expressed in tumor tissues but rarely expressed in the normal liver and can be used as a target for early diagnosis of hepatocellular carcinoma (HCC). Herein, we developed a GPC3-targeted 99mTc-labeled probe for SPECT imaging in HCC. 99mTc-HPG was rapidly radiosynthesized within 20 min with an excellent radiochemical purity (>98%), possessing good stability. Results from in vitro cell binding assays indicated that the binding specificity of 99mTc-HPG to GPC3-positive HepG2 cells was acceptable. For SPECT/CT imaging, the HepG2 tumors were clearly visualized with the highest tumor/muscle ratio (11.55 ± 0.54) at 1 h post-injection, and the tumor uptake of 99mTc-HPG reduced from 2.99 ± 0.15 to 1.17 ± 0.09% ID/g in the blocking study. Convenient preparation, excellent GPC3 specificity in HCC, rapid clearance from normal organs, and good biosafety profiles of 99mTc-HPG warrant further investigations for clinical translation.
研究领域:
医学成像
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肿瘤学
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分子生物学
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核医学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 22
·4577-4586
·
IF 6.331
Yongjia Tang,Haoran Xu,Yaxue Dai,Fang Wang,Wenjing Huang,Peifei Liu,Yueqing Gu
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with limited diagnosis. Mesenchymal epithelial transition factor (c-Met) has become a hot target for cancer diagnosis and therapy, which is overexpressed in HCC. In this study, we labeled a novel c-Met targeting peptide YQ-M3 with a near-infrared fluorescent dye MPA and a radionuclide technetium-99m for HCC detection. YQ-M3-MPA showed high affinity for c-Met positive HepG2 tumor in vitro and higher tumor uptake and higher T/N ratio than GE137-MPA (a positive tracer for c-Met) in HepG2 tumor-bearing mice in vivo by fluorescence imaging. In addition, 99mTc-HYNIC-YQ-M3 also showed significant tumor uptake in vivo through SPECT imaging. These results indicated that c-Met positive tumors were successfully detected via fluorescence and SPECT imaging using YQ-M3-MPA and 99mTc-HYNIC-YQ-M3, respectively, and further suggested that YQ-M3-MPA and 99mTc-HYNIC-YQ-M3 have some possibly potential clinical applications for HCC diagnosis.
研究领域:
肿瘤学
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分子生物学
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医学成像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2018
·Vol. 319
·期 1
·69-73
·
IF 1.181
Duan Xiaoyan,Li Jianbo,Lu Xiaoling
In the field of nanotechnology, DNA-based nanoscale materials have facilitated the construction of DNA polyhedrons with different shapes and sizes by using predictable base pairing and highly tunable conformation. In this study DNA bipyramid nanostructures with one arm chain (T20-DBNs) were successfully prepared in a single annealing procedure. 99m Tc-A20 ssDNA was obtained by radiolabeled DTPA-A20 with 99m Tc, and then 99m Tc-DTPA-DBNs were obtained by hybridizing T20-DBNs with 99m Tc-A20 ssDNA. We focused on studying a method of 99m Tc radiolabeling DNA nanostructures with DTPA as a chelate, and hoped to develop a new SPECT molecular imaging probe based on DNA nanostructures.
研究领域:
纳米技术
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放射医学
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分子影像学
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产品关联
DOI
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 23
·6764-6772
·
IF 6.183
Peifei Liu,Yuanbiao Tu,Ji Tao,Zicun Liu,Fang Wang,Yi Ma,Zhaolun Li,Zhihao Han,Yueqing Gu
Colorectal cancer (CRC) is the third most common cancer worldwide, and the prognosis of CRC is better with an earlier diagnosis. The presence of the gastrin-releasing peptide receptor (GRPR) has been documented in very high numbers on colorectal cancer cells, which makes it an ideal biomarker for the diagnosis of CRC. Bombesin (BBN) peptide analogs have been extensively investigated for the imaging of human cancers with GRPR overexpression. Recently, we have reported a novel GRPR-targeted peptide named the GB-6 peptide. The GB-6 peptide based on BBN7–14 was designed to improve in vivo metabolic stability and decrease intestinal uptake. Meanwhile, GB-6 greatly retained the original GRPR-binding affinity of BBN7–14. In this study, the GB-6 peptide was labeled with radionuclide 99mTc or fluorescent dye for colorectal cancer imaging. In vitro receptor binding was studied in Caco-2 cells, and the GRPR targeting capacity and kinetics in vivo were evaluated using Caco-2 tumor xenografted mice models. In addition, cells and mice were also subjected to the corresponding BBN7–14 conjugations for comparison. The GB-6 peptide exhibited specific GRPR binding in vitro with a high affinity similar to that of BBN7–14. Furthermore, we observed that GB-6 showed higher tumor uptake and displayed lower intestinal activity than corresponding unmodified probe BBN7–14 in Caco-2 tumor-bearing mice. Overall, our studies demonstrated that GB-6 has the potential for early detection of CRC patients, and it may also serve as a valuable tool for non-invasive monitoring of colorectal tumor growth.
研究领域:
医学成像
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肿瘤学
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分子生物学
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药学
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DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·Vol. 48
·期 16
·7300-7307
·
IF 2.7
Chunxiong Lu,Dandan Zhu,Peng Zhou,Kangxia Yu,Yaling Liu,Hongyong Wang,Hao Wu,Jun Wu,Guoqing Han,Pei Zou
Enormous success has been achieved in antitumor therapy with PD-1/PD-L1 inhibitors; however, less than 3 out of 10 patients show clinical benefits. An interesting phenomenon of patients who experienced durable clinical responses to PD-L1 blockade usually being the patients with high PD-L1 expression was noticed. Accordingly, the evaluation of PD-L1 is of great benefit to predict the immunotherapy response against PD-1/PD-L1. A small-molecule single photon emission computed tomography (SPECT) tracer [99mTc]Tc-SG2C-CBM containing a biphenyl moiety was designed and synthesized for the measurement of PD-L1 expression. The radiolabeling yield (RLY) and radiochemical purity (RCP) of [99mTc]Tc-SG2C-CBM were detected to be over 93% under the optimized labeling conditions. [99mTc]Tc-SG2C-CBM was discovered to be equipped with not only good stability but also suitable lipophilicity. In the cellular assays, [99mTc]Tc-SG2C-CBM showed moderate affinity to PD-L1 and 6.87-fold higher uptake in A375-hPD-L1 cells than in A375 cells. Then, the in vivo biodistribution results of the A375-hPD-L1 tumor-bearing mice showed that the radioactivity uptake in tumors was about 2.96 ± 0.76 and 2.31 ± 0.26 fold that in muscles and bones at 2 h post-injection, respectively. SPECT imaging was consistent with the biological distribution of [99mTc]Tc SG2C-CBM, with the uptake being mainly in the liver and less pronounced in tumors. The results of these studies indicate that [99mTc]Tc-SG2C-CBM may be a probe for imaging PD-L1 expression, but further research is needed.
研究领域:
医学影像学
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肿瘤学
·
药物化学
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DOI
高影响因子
Food & Function
·
2018
·Vol. 9
·期 6
·3114-3125
·
IF 3.289
Yu Zhang,Ziming Zheng,Xiawen Yang,Xianglin Pan,Lianglan Yin,Xiao Huang,Qiang Li,Yamin Shu,Qilin Zhang,Kaiping Wang
The aim of this study is to establish a rapid and sensitive method for detecting lentinan (LNT) in biosamples and to evaluate the pharmacokinetics of LNT in mice and rats. A diethylenetriaminepentaacetic acid (DTPA) derivative of LNT (DTPA-LNT) was synthesized first to allow labelling with 99m-technetium (99mTc). After purification and identification, 99mTc-DTPA-LNT was intravenously administered to mice (2 mg kg−1) and rats at different doses (0.5, 2 and 8 mg kg−1). The results showed that the 99mTc-labelling method was suitable for the quantification of the LNT concentration in biological samples, with satisfactory linearity (r2 > 0.998), precision (<7%), accuracy (95.01–104.51%) and total recovery (∼90%). The blood concentration–time profiles of 99mTc-DTPA-LNT were consistent with the two-compartment model and showed a rapid distribution phase and a slow elimination, and no significant difference in the blood level of LNT was found among the tested doses (0.5, 2 and 8 mg kg−1). LNT was predominantly incorporated into the liver and spleen, and there was a small amount of aggregation in the bile, kidneys, lungs and stomach. Approximately 40% of the administered radioactivity was detected in urine and faeces within 24 h post-dosing. In addition, SPECT imaging of 99mTc-DTPA-LNT was performed to visually reveal the pharmacokinetic characteristics of LNT. These findings provide a reference for further study and for use of LNT and other β-glucans.
研究领域:
药代动力学
·
放射化学
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免疫药理学
·
核医学
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生物分析
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）