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.
Urology Surgery Department, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People's Republic of China.
Eur J Nucl Med Mol Imaging. 2022 Jul;49(9):3033-3045. doi: 10.1007/s00259-022-05701-3. Epub 2022 Feb 21.
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.
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.
膀胱癌是人类第五大常见恶性肿瘤。白光膀胱镜检查是膀胱癌诊断的金标准，但一些肿瘤难以可视化，可能会被忽视，导致复发率较高。我们之前开发了一种基于噬菌体展示的肽类近红外成像探针 PLSWT7-DMI，它特异性结合膀胱癌细胞，对动物无毒。在此，我们报告了该探针用于近红外荧光内镜检测膀胱癌的临床研究。
在临床应用之前，我们确认了 PLSWT7-DMI 的纯度、功效、安全性和无毒。本研究纳入了 22 名疑似非肌层浸润性膀胱癌患者。在膀胱内给予探针后，使用我们自行开发的能够在这两种模式之间切换的内窥镜，在白光和近红外成像下对整个黏膜进行成像。对近红外光下发光的病变进行活检，并进行组织病理学检查。与正常组织相比，肿瘤样本的荧光强度增加了 5.1 倍，探针的灵敏度和特异性分别为 91.2%和 90%。常见的诊断挑战，如小卫星肿瘤、原位癌和良性可疑黏膜，都可以被可视化，并与癌症区分开来。此外，在人类中未观察到不良反应。这些首次人体研究结果表明，基于 PLSWT7-DMI 的近红外荧光内镜检查是一种安全有效的膀胱癌检测方法，可能能够进行彻底切除以预防复发。
