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A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Background

Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer.

Results

The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.

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Authors and Affiliations

  1. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China

    Wenting Shang, Kunshan He, Han Deng & Jie Tian

  2. Urology Surgery Department, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China

    Li Peng, Pengyu Guo, Ziyin Chen & Wanhai Xu

  3. NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Yiyuan Street #37, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China

    Li Peng, Pengyu Guo, Ziyin Chen & Wanhai Xu

  4. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Zhongguancun East Road #95, Haidian Dist., Beijing, 100191, China

    Kunshan He, Yu Liu & Jie Tian

Authors
  1. Wenting Shang
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  2. Li Peng
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  3. Kunshan He
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  4. Pengyu Guo
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  5. Han Deng
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  6. Yu Liu
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  8. Jie Tian
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  9. Wanhai Xu
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Contributions

Wenting Shang and Li Peng wrote the manuscript, in addition to designing, performing, and analyzing all experiments. Wenting Shang synthesized and characterized the probe. Kunshan He designed the imaging system. Pengyu Guo assisted with collecting the information on NMIBC patients. Han Deng assisted with the manuscript modification. Yu Liu assisted with the data analysis. Jie Tian and Wanhai Xu designed, supervised, and analyzed all experiments, in addition to assisting with the manuscript preparation.

Corresponding authors

Correspondence to Jie Tian or Wanhai Xu.

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Wenting Shang, Li Peng, Kunshan He, and Pengyu Guo are the parallel first authors.

This article is part of the Topical Collection on Translational research.

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Shang, W., Peng, L., He, K. et al. A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer. Eur J Nucl Med Mol Imaging 49, 3033–3045 (2022). https://doi.org/10.1007/s00259-022-05701-3

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  • DOI: https://doi.org/10.1007/s00259-022-05701-3

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