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授权专利(12项目):
详细

2020  (6 / Total 113 )

  • 1
    Gao S, Jia B, Feng G, Dong C, Du H, Bai L, Zhong Q, Ma Q, Zeng M, Wang F. First-in-human pilot study of an integrin α6-targeted radiotracer for SPECT imaging of breast cancer. Signal Transduct Target Ther. 2020 Aug 11;5(1):147.
  • 2
    Du S, Luo C, Yang G, Gao H, Wang Y, Li X, Zhao H, Luo Q, Ma X, Shi J, Wang F. Developing PEGylated Reversed D-Peptide as a Novel HER2-Targeted SPECT Imaging Probe for Breast Cancer Detection. Bioconjug Chem. 2020 Aug 19;31(8):1971-1980.

    Abstract:

    Human epidermal growth factor receptor-2 (HER2)-enriched breast cancer is characterized by strong invasiveness, high recurrence rate, and poor prognosis. HER2-specific imaging can help screening right patients for appropriate HER2-targeted therapies. Previously, we have developed a 99mTc-labeled HER2-targeted H6 peptide for SPECT imaging of breast cancer. However, the poor metabolic stability and high gallbladder uptake hamper its clinical application. In this study, a retro-inverso D-peptide of H6 (RDH6) was designed to increase the metabolic stability. PEGylation was used to improve its water solubility and in vivo pharmacokinetics. The results showed that the D-amino acids in 99mTc-PEG4-RDH6 brought better metabolic stability than 99mTc-PEG4-H6, thus achieving higher tumor uptake. As the length of the PEG chain increases, the hydrophilicity of the probes gradually increased, which may also be the main cause for the decreased liver uptake. Compared with radiotracers modified by PEG4 and PEG12, 99mTc-PEG24-RDH6 had a comparable tumor uptake and the lowest liver radioactivity. The SPECT imaging demonstrated that 99mTc-PEG24-RDH6 could specifically distinguish HER2-positive tumors from HER2-negative tumors with better imaging contrast, which thus has the potential for clinical screening of HER2-positive breast patients.



  • 3
    Luo Q, Yang G, Gao H, Wang Y, Luo C, Ma X, Gao Y, Li X, Zhao H, Jia B, Shi J, Wang F. An Integrin Alpha 6-Targeted Radiotracer with Improved Receptor Binding Affinity and Tumor Uptake. Bioconjug Chem. 2020 May 20;31(5):1510-1521.
  • 4
    Hou R, Liang X, Li X, Zhang X, Ma X, Wang F. In situ conversion of rose bengal microbubbles into nanoparticles for ultrasound imaging guided sonodynamic therapy with enhanced antitumor efficacy. Biomater Sci. 2020 May 6;8(9):2526-2536.

    Abstract:
    Sonodynamic therapy (SDT) is a prospective therapy for many tumors by activation of sonosensitizers to produce reactive oxygen species (ROS) by ultrasound (US). However, limited generation of ROS and low drug delivery efficiency of sonosensitizers to the tumor tissue still hinder the application of SDT. Herein, an amphiphilic rose bengal (ARB) conjugate was designed to fabricate rose bengal microbubbles (RB-MBs) with high drug-loading contents (∼6.8%) and excellent contrast enhancement capability for US imaging, well suited for detecting tumor location and size. More importantly, RB-MBs could be successfully converted into RB-NPs by local US exposure, resulting in ∼7.5 times higher drug accumulation at the tumor tissue through the sonoporation effect as compared to RB-NPs and RB-MBs without US sonication. Meanwhile, using RB as the MB shell facilitated US energy transfer by the US mediated collapse of MBs through either a sonoluminescence or pyrolysis process; thus, the ROS generation efficiency could be greatly enhanced, resulting in a significantly higher tumor inhibition rate for the RB-MBs + US (∼76.5%) in the HT-29 tumor model as compared to conventional MBs + US and RB-NPs + US (∼23.8% and ∼49.2%), respectively. All these results suggested that this novel sonosensitizer delivery system of RB-MBs combined with US is a powerful strategy for remarkably enhancing SDT therapeutic efficacy with minimal side effects, showing great potential in cancer theranostics.


    Biomater Sci
    DOI: 10.1039/c9bm02046b
    Publication Date:2020 May 6

  • 5
    Wu Y, Li L, Wang Z, Shi J, Hu Z, Gao S, Miao W, Ma Q, Dong C, Wang F. Imaging and monitoring HER2 expression in breast cancer during trastuzumab therapy with a peptide probe 99mTc-HYNIC-H10F. Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2613-2623.
    Abstract:
    Purpose: The novel molecular imaging probe 99mTc-HYNIC-H10F was developed for patient screening and efficacy monitoring of trastuzumab therapy by SPECT imaging of HER2 expression in breast cancer.

    Methods: 99mTc-HYNIC-H10F was developed by labeling H10F peptide with 99mTc following an optimized protocol. Biodistribution and SPECT/CT were performed in mouse models bearing HER2-positive SK-BR3 and HER2-negative MDA-MB-231 human breast cancer xenografts, respectively. The treatment response to trastuzumab was monitored and quantified by SPECT/CT in two HER2-positive breast cancer models (SK-BR3 and MDA-MB-361). The preliminary clinical study was performed in two patients with breast cancer.

    Results: SPECT/CT with 99mTc-HYNIC-H10F showed that the SK-BR3 tumors were clearly visualized, while the signals from MDA-MB-231 tumors were much lower. The tumor uptake of 99mTc-HYNIC-H10F could be blocked by excess unlabeled H10F peptide but not by excess trastuzumab. The growth of two HER2-positive tumors was prominently suppressed at day 11 post-treatment. However, SPECT/CT reflected much earlier therapy response at day 4 post-treatment. The HER2 expression in tumors of breast cancer patients could be detected by 99mTc-HYNIC-H10F SPECT/CT imaging.

    Conclusions: 99mTc-HYNIC-H10F specifically accumulates in HER2-positive tumors. Compared with trastuzumab, 99mTc-HYNIC-H10F binds to a different domain of HER2 antigen, providing new opportunities to monitor HER2 expression levels before/during/after trastuzumab treatment for more effective personalized treatment.

    Keywords: Breast cancer; HER2; SPECT/CT; Therapy monitoring; Trastuzumab.
  • 6
    Wang Y, Zhang C, Lai J, Zhao Y, Lu D, Bao R, Feng X, Zhang T, Liu Z. Noninvasive PET tracking of post-transplant gut microbiota in living mice. Eur J Nucl Med Mol Imaging. 2020 Apr;47(4):991-1002. doi: 10.1007/s00259-019-04639-3. Epub 2020 Jan 2.

    Abstract:


    Purpose: The role that gut microbiota plays in determining the efficacy of the anti-tumor effect of immune checkpoint inhibitors is gaining increasing attention, and fecal bacterial transplantation has been recognized as a promising strategy for improving or rescuing the effect of immune checkpoint inhibition. However, techniques for the precise monitoring of in vivo bacterial behaviors after transplantation are limited. In this study, we aimed to use metabolic labeling and subsequent positron emission tomography (PET) imaging to track the in vivo behaviors of gut bacteria that are responsible for the efficacy of anti-PD-1 therapy in living mice.

    Methods: The antitumor effect of anti-PD-1 blockade was tested in a low-response 4T1 syngeneic mouse model with or without fecal transplantation and with or without broad-spectrum antibiotic imipenem treatment. High-throughput sequencing analyses of 16S rRNA gene amplicons in feces of 4T1 tumor-bearing mice pre- and post-anti-PD-1 treatment were performed. The identified bacteria, Bacteroides fragilis (B. fragilis), were labeled with 64Cu and fluorescence dye by the metabolic labeling of N3 followed by click chemistry. In vivo PET and optical imaging of B. fragilis were performed in mice after oral gavage.

    Results: The disturbance of gut microbiota reduced the efficacy of anti-PD-1 treatment, and the combination of B. fragilis gavage and PD-1 blockade was beneficial in rescuing the antitumor effect of anti-PD-1 therapy. Metabolic oligosaccharide engineering and biorthogonal click chemistry resulted in successful B. fragilis labeling with 64Cu and fluorescence dye with high in vitro and in vivo stability and no effect on viability. PET imaging successfully detected the in vivo behaviors of B. fragilis after transplantation.

    Conclusion: PET tracking by metabolic labeling is a powerful, noninvasive tool for the real-time tracking and quantitative imaging of gut microbiota. This strategy is clinically translatable and may also be extended to the PET tracking of other functional cells to guide cell-based adoptive therapies.

    Keywords: 64Cu; Gut microbiota; Metabolic labeling; Molecular imaging; PET tracking.

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