TMIC-42. DEVELOPMENT OF NOVEL SPRAY-TYPE FLUORESCENT PROBES FOR BRAIN TUMORS

Abstract PURPOSE: 5-Amino Levulinic Acid (5-ALA) is commonly used as an intraoperative aid in malignant glioma surgery, which has been proved to be effective for more radical tumor resection and better patient prognosis. However, there are some limitations in its use, such as false positivity, false negativity, and inability of re-administration. We aim to develop a novel fluorescent labeling system, which can be repeatedly administered by spray during surgery, using hydroxymethyl rhodamine green (HMRG) and 2 methyl siliconrhodamine (2MeSiR600) as host fluorescent nuclei originally designed at our university for cancer detection, complementing 5-ALA. METHODS Four groups of homogenized samples were prepared from frozen tissues which consisted of 10 peritumoral specimens, 5 glioblastomas, 5 astrocytomas, and 5 oligodendrogliomas. Probe screening was performed using the fluorescent probe library comprised of HMRG and 2MeSiR600 host fluorescent nuclei combined with various types of dipeptides. More than 720 kinds of fluorescent probes were applied to homogenized lysates. According to the fluorescence intensity measured over time after application, probes exhibiting strong focal fluorescent marks with large difference between peritumor and tumor tissues were selected as valid probes. The selected probes were then validated by the experiment using fresh specimens. RESULTS & DISCUSSION: The top probes were selected based upon the experiments using homogenized lysates as well as fresh specimens. They were validated prospectively with more surgical cases. With the combination of the two types of fluorescent host nuclei, glioblastoma can be identified in multi-color. CONCLUSION Fluorescent probes with HMRG and 2MeSiR 600 host nuclei can be effective for intraoperative detection of glioma.