Clinical Research Directory

Novel Humanized Ferritin-Based NIR Fluorescent Probe for Identifying Sentinel Lymph Node Metastasis in Early Gastric Cancer

With the widespread adoption of early cancer screening, the proportion of early gastric cancer (EGC) in China has been gradually increasing. The primary treatments for EGC are endoscopic and surgical interventions. For EGC invading the submucosal layer, the lymph node metastasis rate is approximately 20%. In clinical practice, subtotal gastrectomy combined with D2 lymphadenectomy is commonly performed to achieve radical tumor resection, resulting in up to 80% of patients undergoing unnecessary lymph node dissection. Sentinel lymph nodes (SLNs), which are the first potential sites along the lymphatic drainage pathway from the primary tumor to receive cancer cells, can effectively represent the status of lymphatic metastasis. As gastric cancer surgery evolves toward minimally invasive, precise, and individualized approaches, there is an urgent clinical need for a safe and effective SLN mapping technique to intraoperatively distinguish between benign and malignant SLNs, thereby avoiding unnecessary lymphadenectomy and improving patient prognosis. Currently, indocyanine green (ICG) is the only clinically approved near-infrared (NIR) fluorescent dye and is relatively widely used. However, it lacks targeting specificity, diffuses too rapidly, and has difficulty identifying micrometastases in SLNs. Therefore, we aimed to enhance ICG's targeting ability toward metastatic tumor cells to increase fluorescence signal intensity in malignant SLNs, enabling intraoperative differentiation between benign and malignant SLNs and reducing unnecessary lymph node dissection. Considering the high heterogeneity of tumor cells and the molecular diversity among metastatic foci within malignant SLNs, our team innovatively proposed a multi-target probe design to improve targeting capability against heterogeneous tumor cells. Based on molecular imaging technology combined with near-infrared (NIR) imaging, we developed a humanized ferritin-based probe (VE/CX-FTn) targeting metastatic lymph nodes. Previous studies have confirmed the effective identification of metastatic lymph nodes by the VE/CX-FTn probe. To further validate the effectiveness of this probe in identifying SLN metastasis in early gastric cancer with a low lymph node metastasis rate, this study plans to use residual early gastric cancer tissues obtained from post-surgical resections to evaluate the probe's imaging capability for SLNs. Furthermore, a prospective clinical sample cohort study will be conducted to verify its diagnostic efficacy for metastatic lymph nodes of varying sizes. The aim is to demonstrate that our developed probe can guide the identification of SLNs in early gastric cancer and assist in determining the presence of SLN metastasis, thereby reducing unnecessary lymphadenectomy and improving patient prognosis. This study employs a novel NIR fluorescent molecular probe, VE/CX-FTn-ICG, based on humanized ferritin, with the objective of investigating its effectiveness in distinguishing between benign and malignant sentinel lymph nodes in early gastric cancer. Using this probe, we have already demonstrated that VE/CX-FTn-ICG enables precise differentiation between benign and malignant lymph nodes in animal models. The probe specifically binds to tumor cells, exhibiting high targeting specificity and imaging capability, thereby providing real-time and accurate intraoperative imaging of SLNs for early gastric cancer surgery. A further goal of this study is to validate the application efficacy of this targeted probe in distinguishing between benign and malignant SLNs using ex vivo human early gastric cancer tissue samples. This aims to provide a reliable auxiliary tool for intraoperative SLN biopsy in early gastric cancer, assisting in avoiding unnecessary lymph node resection for patients, and ultimately improving surgical outcomes and patient prognosis.

Novel Humanized Ferritin-based NIR Fluorescent Molecular Probe for Identifying Tumor Margins in Gastric Tissue

Radical surgery remains the primary treatment for gastric cancer, but intraoperative tumor margin assessment relies on surgeons' visual inspection, limiting accuracy. There is thus an urgent clinical need for real-time visualisation of tumour margins. In recent years, near-infrared (NIR) fluorescence imaging has emerged as a critical tool for precision tumor resection. However, existing probes like indocyanine green (ICG) lack tumor-targeting specificity. Ferritin (FTn), with its unique nanocage structure, excellent biosafety, and well-defined in vivo behavior, presents an attractive platform for targeted molecular probes. Yet, translational challenges persist, including animal model limitations and clinical validation bottlenecks. To address this, our study employs freshly resected human gastric tissue in an ex vivo perfusion system, simulating the circulatory dynamics of the humanized ferritin-based probe FTn-ICG in vivo. Using a prospective clinical sample cohort, we aim to validate its diagnostic efficacy in delineating gastric cancer margins, ultimately overcoming the critical barrier of precise tumor boundary identification.

HER2-PET as a Precision Imaging Tool for Treatment With HER2-ADC in HER2-expressing mBC

This is a prospective, multi-center, open-label, exploratory diagnostic phase II imaging trial for patients with metastatic breast cancer with at least one line of systemic therapy. The overarching aim of the HER2-Ex PET trial is to study the role of precision imaging utilizing positron emission tomography (PET) with the HER2-specific tracer \[68Ga\]Ga-ABY-025 (hereafter referred to as HER2-PET) in enhancing treatment planning for patients with metastatic HER2-expressing breast cancer Patients will be allocated based on HER2-status on PET and biopsy. Patients with HER2-expressing lesions in a fresh or archived tumour biopsy will be treated with T-DXd. The study hypothesis is that PET/CT precision imaging with a contemporary HER2-radiotracer (\[68Ga\]Ga-ABY-025) can be used and can lead to a potentially better identification of patients who benefit from T-DXd treatment, thereby achieving improved treatment responses as well as fewer side effects. This study's diagnostic approach provides a more individualized treatment strategy. Additionally, this study can potentially give us a better biological understanding of HER2-expressing mBC.

Molecular Breast Imaging (MBI)-Guided Biopsy

The goal of this pilot clinical trial is to demonstrate supplemental screening MBI (molecular breast imaging) in women with dense breasts. The main questions it aims to answer are: * Does screening MBI find more cancer than screening DBT (3D mammography, digital breast tomosynthesis? * Does screening MBI result in more call-backs for biopsy than DBT? * How well does MBI-guided biopsy conform with pathology reports? Researchers will compare screening MBI to screening DBT to see if MBI is more sensitive to detecting cancer in women with dense breasts. Participants will * Receive both screening DBT and screening MBI * Receive either DBT-guided or MBI-guided biopsy (randomly assigned), if required by the screening images

68Ga-FAPI-46 in Staging of Pancreatic Adenocarcinoma

This clinical study investigates the use of a new imaging technique called 68Ga-FAPI-46 PET/CT in people with pancreatic ductal adenocarcinoma (PDAC), a type of cancer known for its rapid progression, late diagnosis, and poor survival rate. One of the main challenges with pancreatic cancer is that standard images like MRI and CT, while helpful, are not always able to clearly show how far the cancer has spread or where exactly the tumor ends. This can make surgery and treatment planning more difficult and less precise. The new image technique being studied, 68Ga-FAPI-46 PET/CT, works by injecting a small and safe amount of a radioactive substance into a vein. This substance travels through the body and attaches to a specific protein called FAP, which is found in large amounts in the tissue that surrounds many pancreatic tumors. By sticking to this protein, the tracer highlights not only the tumor but also the surrounding area that may be affected by the cancer. This results in very detailed images that may show the tumor more clearly than other techniques. Each participant in the study will receive a single injection of the tracer, and about an hour later they will have the PET/CT scan. The scan itself is quick, painless, and non-invasive, and takes about 20 minutes. A few days later, participants will receive a follow-up phone call to check if they experienced any side effects, though previous studies with over 1,000 people have shown the tracer to be very safe. The purpose of the study is to find out whether this new technique provides more useful and accurate information than the standard images currently used. It may help better detect the size of the tumor, see if it has spread to other parts of the body, and give doctors a clearer idea of how to plan surgery. This could make it easier to remove the tumor completely and choose the most effective treatment for each patient. This pilot study is being conducted at Lausanne University Hospital (CHUV) with 20 adult participants over two years. CHUV is the first hospital in Switzerland to offer this kind of scan. If the study is successful, this scan may become a regular part of care for people with pancreatic cancer and could also be used in other cancers in the future.