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
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药物化学
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DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Pengfei Dou,Jinglin Wang,Yamin Shu,Fang Cheng,Gang Nie,Li Luo,Zhijing Wu,Ziming Zheng,Yongkang Gai,Junxi Liu,Yan Liu,Yinxing Zhou,Yu Zhang,Xiaoli Lan,Kan Ding,Kaiping Wang
Natural polysaccharides are attracting increasing attention due to their excellent pharmacological properties and low toxicity. However, the clinical translation of these biomacromolecules has been hindered by a lack of pharmacokinetic studies. Polysaccharide labelling presents a promising method for performing pharmacokinetic investigations on polysaccharides. The combination of radioisotopic labelling and high-performance gel permeation chromatography (HPGPC) has not yet been applied to the detection of polysaccharides in biological samples. Here, Dendrobium officinale polysaccharides (DOP) were selected as model polysaccharides. DOP and radiolabelling of DOP ( 99m TC-DTPA-DOP) were prepared and characterized. Then, HPGPC with a radio-HPLC flow detector (radioHPGPC) was used to analyse 99m TC-DTPA-DOP in biological samples for the first time. The detection method was demonstrated to exhibit good linearity (R 2 > 0.997), sensitivity (LLOD <100 nCi, and 62.99 ng/mL for the Conc of DOP), specificity, and recovery rate (>90 %). The blood concentration and distribution in major organs after oral and intravenous administration were studied. The results showed that the bioavailability of DOP was 2.68 %. This method is superior to γ counting or liquid scintillation counting because radioHPGPC could not only eliminate the impact of free 99m Tc and quantity the DOP tracer but also qualitatively analyse the metabolism during absorption and distribution. This study provides detailed pharmacokinetic profiles of DOP and a practical method for labelling and pharmacokinetic studies of other polysaccharides with high molecular weight.
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Zuojie Li,Lina Diao,Peiwen Han,Qingna Xiao,Dajie Ding,Junhong Feng,Jianyong Jiang,Junbo Zhang
Radiolabeled human epidermal growth factor receptor 2 (HER2) tracers are important tools for the accurate clinical diagnosis and treatment of HER2-positive tumors. The aim of this study was to investigate the potential of small molecule inhibitors (lapatinib) as target groups for novel radiotracers targeting HER2. Twelve stable radiotracers were prepared by chelation with different coligands. The relationships between the linker and the combination of coligands with pharmacodynamics were systematically evaluated. [99mTc]Tc-Lapa-HYNIC-TPPTS exhibits the most favorable pharmacokinetic properties, as it can stably bind to the active pocket of the HER2 protein. Both in vitro and in vivo studies demonstrated its high targeting specificity toward HER2. SPECT images of [99mTc]Tc-Lapa-HYNIC-TPPTS in HER2-positive model mice revealed that it can effectively locate tumors. This study is the first attempt at a 99mTc-labeled small-molecule inhibitor tracer targeting HER2, showing great potential for applications in the diagnosis of HER2-positive cancers.
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DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Ruihua Chen,Hao Deng,Junpeng Jiang,Daoyang Han,Gang Shao,Hailong Wang,Rui Zhang,Chao Ma
To overcome the problem of insufficient molybdenum adsorption capacity of commercially utilized alumina in 99 Mo/ 99m Tc generator, UiO-66(Ce)@MXene composites as potential molybdenum adsorbents were successfully prepared via in-situ growth method in this work. The adsorption performance and adsorption mechanism were investigated. The results indicate that the UM3 possesses superlative adsorption behavior compared to the other two samples. The adsorption kinetics are well described by the quasi-second-order model and the adsorption reaches equilibrium within 30 min. The adsorption isotherm can be well fitted with the Langmuir model, displaying the maximum molybdenum adsorption capacity of 833 mg/g at pH 3, superior to other reported adsorbents. The adsorption capacity manifests that polymolybdates are captured by the hydroxyl groups on MXene through hydrogen bonds. The monomolybdates can diffuse into micropores and are adsorbed on adsorption sites, e.g. missing-linker defects and Ce-OH groups. Consequently, the constructed hierarchical frameworks promote molybdenum adsorption and increase adsorption capacity significantly. The unrivalled adsorption performance of UiO-66(Ce)@MXene composites as molybdenum adsorbents have promising potential for the application in 99 Mo/ 99m Tc generator.
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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
·
肿瘤学
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DOI
PubMed
高影响因子
TALANTA
·
2022
·
IF 6.556
Xin Gao,Haoran Xu,Zhuoyi Ye,Xin Chen,Xin Wang,Qi Chang,Yueqing Gu
The 5-year survival rate for pancreatic adenocarcinoma (PA) is less than 10%, making it one of the most lethal forms of cancer. Early-stage diagnosis and resection of the incipient lesions could increase the 4-year survival rate of PA up to 78%. Platelet-derived growth factor receptor β (PDGFRβ), an oncogenic key regulator for migration, proliferation and angiogenesis of cancer cells, has been proved to be aberrantly expressed in the majority of PA. Herein, by amino acid substitution strategy and surface plasmon resonance (SPR) analysis, we designed a novel PDGFRβ-targeting peptide (YQGX-10) with high affinity ( K d = 227.7 nM) and coupled it with a near-infrared fluorescent (NIRF) dye MPA for precisely detection of PA. Great binding affinity and specificity were displayed in a series of in vitro assays. NIRF imaging experiments demonstrated that the synthesized probe could be highly accumulated in xenograft and orthotopic BxPC-3 tumors and provide favorable tumor contrast in the mice, offering a potential novel approach for the early diagnosis of PA. Moreover, YQGX-10 could visualize tumor boundaries and minor lesions in BxPC-3 xenograft mice, shedding a new light on NIRF-guided tumor resection of PA. In addition, we successfully constructed the radioactive probe 99m Tc-HYNIC-YQGX-10 for the diagnosis of PA with high specificity and sensitivity. In summary, the probe warrants further exploration for clinical translation in the early diagnosis and NIRF-guided surgery of PA.
研究领域:
肿瘤学
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分子影像学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Yibin Yu,Chong Huang,Fen Chen,Weisan Pan,Ling Zhang
Integration of diagnostic and therapeutic modalities into a single nanoplatform can play an important role in personalized cancer therapy. In this work, an all-in-one theranostic nanoplatform (HPCT nanomicelles) for breast cancer was fabricated, composed of the synthetic polymer hyaluronan- b -poly(ε-caprolactone) (HA-PCL), drug curcumin (Cur) and adjuvant tocopheryl polyethylene glycol succinate (TPGS). HPCT nanomicelles presented adequate drug loading efficiency, excellent stability, and attractive hyaluronidase-sensitive release features. Imaging agent radionuclide 99m Tc was loaded into HPCT nanomicelles (denoted as 99m Tc-HPCT nanomicelles) and in vivo SPECT/CT imaging verified the HA-based nanomicelles could actively target breast cancer in mice. In vivo anti-tumor pharmacodynamic studies indicated that HPCT nanomicelles exhibited desirable anti-tumor efficacy with favorable biosafety. 99m Tc-HPCT nanomicelles, integrating imaging and therapeutic modalities, have the promising potential to be an all-in-one theranostic nanoplatform for breast cancer.
研究领域:
癌症治疗
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纳米技术
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药学
·
诊断成像
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Jie An,Xinyi He,Huizhu Ma,Yanglei Li,Yayuan Li,Xinyu Zhang,Qizhi Shuai,YinMeng Wang,Wen Liu,Weihua Li,Hongliang Wang,Zhifang Wu,Sijin Li
Radionuclide therapy (RNT) is an effective method for the clinical precise treatment of cancer. However, the uneven dose distribution and rapid metabolism of nuclides limit the effective killing of tumors. To overcome the limitations of radionuclide therapeutic approaches, combining different therapeutic strategies to treat cancer has manifested great promise in basic and clinical research. Here, a new combination therapy strategy was developed to combine radionuclide therapy, sonodynamic therapy and photothermal therapy (RNT-SDT-PTT) under radionuclide imaging guided achieve highly effective combination therapy. We prepared a polydopamine-modified Au nanostar (AN), then loaded with the acoustic sensitizer protoporphyrin (IX) and labeled with diagnostic ( 99m Tc) or therapeutic ( 131 I) radionuclides ( 131 I/ 99m [email protected] /IX) for the precise diagnosis and treatment of pancreatic cancer. After intratumor administration, single photon emission computed tomography imaging showed that the nanocarriers were mostly retained in the tumor compared to free radionuclide. As well as using near-infrared light to trigger PTT and ultrasound with high penetration depth to activate IX to generate reactive oxygen species achieved SDT of tumor. The ultimate significantly improved the inhibitory effects by the RNT-SDT-PTT combined therapy for pancreatic cancer. Therefore, this study proposes an effective radionuclide combination therapy regimen consisting of three widely used treatments, offering promising prospects for the future of oncology.
研究领域:
肿瘤学
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核医学
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诊疗一体化
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纳米技术
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 9
·2682-2693
·
IF 6.183
Yuanbiao Tu,Ji Tao,Fang Wang,Peifei Liu,Zhihao Han,Zhaolun Li,Yi Ma,Yueqing Gu
Pancreatic cancer has a high mortality rate and efforts towards diagnosis and therapy at an early stage are particularly appealing. Recently, a small peptide, BBN7–14, has attracted much attention for its specific binding ability to gastrin releasing peptide receptor (GRPR), which is highly overexpressed in various types of cancer, including pancreatic cancer. However, its poor stability in vivo restricts its direct clinical application. Herein, by rational design and transformation of BBN7–14, a novel six-amino acid peptide, GB-6, which maintains a specific GRPR-binding feature and exhibits enhanced stability in vitro and in vivo, was designed. Competitive binding with BBN7–14 and cellular uptake related to GRPR expression levels verified the specific affinity of GB-6 to GRPR. Additionally, this novel peptide was conjugated with near-infrared dye and the radionuclide 99mTc for pancreatic cancer diagnosis in cells and in vivo. Surprisingly, despite having the same cellular affinity as BBN7–14, GB-6 showed much higher pancreatic cancer-targeting ability than BBN7–14 by both fluorescence imaging and radionuclide imaging. It was proven that this strange phenomenon was attributed to the distinct in vivo stability of GB-6 and its more favorable pharmacokinetic properties and metabolic stability relative to BBN7–14. Altogether, this novel peptide GB-6, with GRPR-targeting ability and enhanced stability, is a more promising candidate for the clinical diagnosis of pancreatic cancer.
研究领域:
肿瘤学
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分子生物学
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药学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Xia Yang,Jing Wang,Zhikai Ding,Qingchuan Lin,Liangang Zhuo,Wei Liao,Yan Zhao,Yue Feng,Yue Chen,Hongyuan Wei,Yuchuan Yang
Hyaluronan (HA) have been widely used as the ideal biomaterials. It is important to understand their degradation and distribution for better optimization. From a new aspect of using radiotracers, we designed the HA-tyramine-bisphosphonate derivative for dual-labelling with two radionuclides ( 99m Tc and 131 I) simultaneously for in vitro and in vivo tracking. This dual-radiolabelled HA derivative can still be non-covalently crosslinked by hydroxyapatites to form injectable gel. The excellent properties of the gel, such as robust, biodegradable, and self-healing capacity were maintained. We firstly proved the possibility to distinguish different radionuclides in the degraded gel using the high-resolution gamma-ray spectrometry. The radiolabelled gel showed lower toxicity than pure hydroxyapatites against various cell lines, while the in vivo results proved that the 99m Tc/ 131 I-labelling of the gel was safe and stable enough for imaging and quantitatively tracking. The present method can also be applied for the development of dual-radiolabelled gels from other polysaccharides.
研究领域:
生物材料
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放射药学
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药学
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生物医学工程
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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）