Indocyanine Green

Calcium ions are essential for cells, but can be toxic in higher concentrations. A team of researchers has now designed and prepared a combination drug that kills tumor cells by modulating the calcium influx into the cell. An external calcium source is not necessary because only the calcium ions already present in the tumor tissue are used, according to a new study. Calcium ions are essential for cells, but can be toxic in higher concentrations. A team of researchers has now designed and prepared a combination drug that kills tumor cells by modulating the calcium influx into the cell. An external calcium source is not necessary because only the calcium ions already present in the tumor tissue are used, according to the study published in the journal Angewandte Chemie. Biological cells need calcium ions, among other things, for the proper functioning of the mitochondria, the powerhouses of the cells. However, if there is too much calcium, the mitochondrial processes become unbalanced and the cell suffocates. A research group led by Juyoung Yoon of Ewha Womens University in Seoul, South Korea, together with teams from China, has now taken advantage of this process and developed a synergistic antitumor drug that can open calcium channels and thus trigger a deadly calcium storm inside the tumor cell. The researchers targeted two channels, the first one in the outer membrane, and the other was a calcium channel in the endoplasmic reticulum, a cell organelle that also stores calcium ions. The channel located in the outer membrane opens when it is exposed to a large amount of reactive oxygen species (ROS), while the channel in the endoplasmic reticulum is activated by nitric oxide molecules. To generate the ROS that open the outer membrane calcium channel, the researchers used the dye indocyanine green. This bioactive agent can be activated by irradiation with near-infrared light, which not only triggers reactions that lead to ROS, but it also heats up the environment. The team explains that the high local temperature activates the other active agent, BNN-6, to release nitric oxide molecules that open the channel in the endoplasmic reticulum. Following successful trials in tumor cell lines, the team tested an injectable formulation in tumor-implanted mice. To create a biocompatible combined drug, the researchers loaded the active ingredients into tiny modified porous silica beads that are not harmful to the body, but can be recognized by tumor cells and transported into the cell. After injecting the beads into the bloodstream of the mice, the researchers observed that the drug accumulated in the tumor. Exposure to near-infrared light successfully triggered the mechanism of action, and the tumor disappeared after a few days in mice that received the preparation. The authors emphasize that this ion influx approach may also be useful in related biomedical research areas where a similar mechanism could activate ion channels different from calcium in order to find new therapeutic approaches.

MINNEAPOLIS, Minn., January 28, 2024 – Vergent Bioscience, a clinical-stage biotechnology company developing tumor-targeted imaging agents, announced new data presented today at the 60th Annual Meeting of The Society of Thoracic Surgeons (#STS24). The data demonstrate that VGT-309, the company’s investigational tumor-targeted fluorescent imaging agent, visualizes primary and metastatic tumor tissue in the lung during surgery. The findings reinforce results from earlier clinical trials of VGT-309 which suggest the agent may help surgeons see difficult-to-find and previously undetected tumors in real time, ensuring all tumor tissue is removed during minimally invasive (MIS) and robotic-assisted lung cancer surgery. “The data presented today at STS 2024 suggest that VGT-309 could help support more confident and reliable removal of a wide breadth of cancers in the lung that would otherwise be missed during minimally invasive and robotic surgery,” said John Santini, Ph.D., president and chief executive officer at Vergent Bioscience. “We look forward to the results from our ongoing, Phase 2 multi-center VISUALIZE study, which will provide further insight regarding the potential promising impact of VGT-309 for both cancer patients and surgeons.” The VGT-309 Phase 2* efficacy study evaluated the frequency that intraoperative molecular imaging (IMI) improved surgical outcomes in 40 individuals with suspected or proven cancer in the lung who were eligible for surgery. The primary efficacy endpoint was the proportion of patients with at least one clinically significant event. Clinically significant events were defined as localization of lesions not found by standard surgical techniques, identification of synchronous and occult cancers, and inadequate surgical margin. Each patient in the study received VGT-309 preoperatively through intravenous infusion. Following an attempt to localize tumors using standard surgical techniques, investigators used a commercially available near infrared (NIR) endoscope to assess the presence of tumor tissue, which was then confirmed by pathology. Of the 40 participants administered VGT-309 who underwent the standard-of-care surgical resection for suspected lung cancer, 17 (42.5%) had at least one clinically significant event. VGT-309 with NIR fluorescence imaging visualized a range of primary and metastatic tumor types intraoperatively, including adenocarcinoma in situ, invasive adenocarcinoma, lymphoma, colorectal cancer, neuroendocrine tumors, sarcomas, and squamous cell carcinoma. VGT-309 was safe and well tolerated in this study, with no infusion reactions and no drug-related serious adverse events. “Minimally invasive surgery has become standard of care for many cancer surgeries, but surgeons’ ability to see and remove all tumor tissue during these procedures is often hindered by poor visualization,” said Sunil Singhal, M.D., lead investigator and chief of the division of thoracic surgery in the Perelman School of Medicine at University of Pennsylvania. “The data from the VGT-309 Phase 2 efficacy study are encouraging, reinforcing the agent’s potential to help fill this critical gap.” *This clinical trial ( ClinicalTrials.gov Identifier: NCT05400226) was supported by the National Cancer Institute of the National Institutes of Health under award number R44CA277890. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About VGT-309 VGT-309 is a tumor-targeted imaging agent designed to enable a complete solution for optimal tumor visualization during open, minimally invasive surgery (MIS), and robotic-assisted surgical procedures. VGT-309 is delivered to patients via a short infusion several hours before surgery. Invented in Professor Matt Bogyo’s Lab at Stanford University School of Medicine, the molecule binds tightly (i.e., covalently) to cathepsins, a family of proteases that are overexpressed across a broad range of solid tumors. This approach, if successful, provides distinct clinical advantages and positions VGT-309 as an ideal tumor imaging agent. VGT-309’s imaging component is the near infrared (NIR) dye indocyanine green (ICG), which is compatible with all commercially available NIR intraoperative imaging systems that support MIS technologies and is the preferred dye to minimize confounding background autofluorescence. About Vergent Bioscience, Inc. Vergent Bioscience is a clinical-stage biotechnology company that is helping surgeons realize the full potential of minimally invasive and robotic surgery by significantly improving the visibility of tumors. Vergent’s lead compound, VGT-309, is a tumor-targeted fluorescent imaging agent designed to enable surgeons to see difficult-to-find or previously undetected tumors in real-time during surgery, so that they can ensure all tumor tissue is removed. The company is first evaluating VGT-309 for cancer in the lung, with the potential to expand its application to a wide range of solid tumors. Vergent Bioscience is a privately held company based in Minneapolis, MN. Vergent Bioscience Australia Pty Ltd is a wholly owned subsidiary of Vergent Bioscience. Source: Vergent Bioscience, Inc. Posted: January 2024 More news resources FDA Medwatch Drug Alerts Daily MedNews News for Health Professionals New Drug Approvals New Drug Applications Clinical Trial Results Generic Drug Approvals Subscribe to our newsletter Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.