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

Abstract

Bladder cancer is the fth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are di cult to visualize and can be overlooked, resulting in high recurrence rates. Method:We developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds speci cally to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared uorescence endoscopic detection of bladder cancer. ResultsThe purity, e cacy, safety, and nontoxicity of PLSWT7-DMI were con rmed 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 uorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and speci city 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. Further, no adverse effects were observed in humans. ConclusionThese rst-in-human results indicate that PLSWT7-DMI-based near-infrared uorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.

Precise diagnosis and treatment of non-muscle invasive bladder cancer - A clinical perspective

“…CD44 is a cancer stem cell marker, which is highly expressed on the cell membrane of BCa and participates in cell adhesion, cell migration, tumor progression and metastasis ( 73 ). The results of the first human experiment showed that the fluorescence-guided imaging based on the NIR fluorescence probe targeting CD44v6 is a safe and effective method, which can improve the detection rate of BCa, and may enable complete resection to prevent recurrence ( 74 ). The pH-low insertion peptide (pHLIP) is a C-helix derived from the bacteriorhodopsin protein that targets the acidic microenvironment in the tumor matrix ( 75 ).…”

Intraoperative fluorescence molecular imaging accelerates the coming of precision surgery in China

“…There is an urgent need of precision surgery. We can foresee that the application of intraoperative FMI would be rapidly expanded [ 93 , 136 ]. So far, the clinical value of non-specific fluorophores has been widely explored.…”

Gastric cancer specific drug delivery with hydrophilic peptide probe conjugation

“…7 Preclinical experiments and clinical trials have been conducted based on the synthesis of peptides created with fluorescent phage display. 8–10 In a separate example from gastroenterology, molecular imaging with fluorescently labeled peptides has been developed to guide biopsy targeting high-grade dysplasia in Barrett's esophagus and to detect serrated colon polyps. 11–13…”

“…7 Preclinical experiments and clinical trials have been conducted based on the synthesis of peptides created with fluorescent phage display. [8][9][10] In a separate example from gastroenterology, molecular imaging with fluorescently labeled peptides has been developed to guide biopsy targeting high-grade dysplasia in Barrett's esophagus and to detect serrated colon polyps. [11][12][13] The leucine-rich G protein-coupled receptor 5 (LGR5) belongs to the glycoprotein receptor super-family, characterized by a large, leucine-rich extracellular domain and the peptide N-terminus.…”