Wenting Shang1, Li Peng2,3, Kunshan He1,4, Pengyu Guo2,3, Han Deng1, Yu Liu4, Ziyin Chen2,3, Jie Tian5,6, Wanhai Xu7,8. 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. 2. Urology Surgery Department, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People's Republic of China. 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. 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. 5. 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. jie.tian@ia.ac.cn. 6. 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. jie.tian@ia.ac.cn. 7. Urology Surgery Department, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People's Republic of China. xuwanhai@163.com. 8. NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Yiyuan Street #37, Nangang District, Harbin, Heilongjiang, 150001, People's Republic of China. xuwanhai@163.com.
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.
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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