Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 22
·4577-4586
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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
Molecular Therapy-Nucleic Acids
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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 MEDICINAL CHEMISTRY
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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
Food & Function
·
2018
·Vol. 9
·期 6
·3114-3125
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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
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放射化学
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免疫药理学
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核医学
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生物分析
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DOI
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
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2018
·Vol. 316
·期 2
·685-690
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IF 1.181
Song Hu,Wang Yunhan,Wang Jing,Wang Guanquan,He Jiaheng,Wei Hongyuan,Luo Shunzhong
For the superiority of graphene quantum dots (GQDs) in bioimaging and drug delivery carrier, GQDs bring new opportunities for theranostics of diseases. In this study, GQDs were successfully prepared and labeled with 131 I. The in vitro properties, biodistribution and SPECT imaging of 131 I-GQDs were investigated. The uptake of 131 I-GQDs at tumor sites can be clearly observed via SPECT imaging and T/B and T/M ratios increase with increasing time, which can contribute to enhanced permeability and retention (EPR) effect.
研究领域:
核医学
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放射学
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Deliang Zhang,Rongqiang Zhuang,Jindian Li,Yuting Lv,Xia Yang,Weimin Pan,Xianzhong Zhang
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with poor prognosis. Evidence has shown that vimentin is a key regulator of lung fibrogenesis. 99mTc-labeled N-acetylglucosamine-polyethyleneimine (NAG-PEI), a vimentin-targeting radiotracer, was used for the early diagnosis of IPF, and NAG-PEI was also used as a therapeutic small interfering RNA (siRNA) delivery vector for the treatment of IPF in this study. Single-photon emission-computed tomography (SPECT) imaging of bleomycin (BM)- and silica-induced IPF mice with 99mTc-labeled NAG-PEI was performed to visualize pulmonary fibrosis and monitor the treatment efficiency of siRNA-loaded NAG-PEI, lipopolysaccharide (LPS, a tolerogenic adjuvant), or zymosan (ZYM, an immunostimulant). The lung uptakes of 99mTc-NAG-PEI in the BM- and silica-induced IPF mice were clearly and directly correlated with IPF progression. The lung uptake of 99mTc-NAG-PEI in the NAG-PEI/TGF-β1-siRNA treatment group or LPS treatment group was evidently lower than that in the control group, while the lung uptake of 99mTc-NAG-PEI was significantly higher in the ZYM treatment group compared to that in the control group. These results demonstrate that NAG-PEI is a potent MicroSPECT imaging-guided theranostic platform for IPF diagnosis and therapy.
研究领域:
肺病学
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放射学
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分子生物学
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诊疗学
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产品关联
DOI
PubMed
高影响因子
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