Photodynamic therapy of malignant brain gliomas

Abstract

Treatment of malignant gliomas of the brain remains a serious problem on a global scale, despite intensive research into the causes and mechanisms of their progression. When using traditional surgical approaches and imaging methods tumor cell infiltrates may be overlooked, as a result of which, malignant gliomas relapse often occurs near the marginal region of the surgical cavity. A method that allows visual identification of tumor tissue and at the same time provides an opportunity to selectively destroy it is photodynamic therapy (PDT) ‒ a two-stage treatment that includes the introduction (intravenous, intraperitoneal, local or oral) of a light-sensitive chemical agent (photosensitizer (PS)) followed by its activation at a certain wavelength of light.The principle of PDT is based on the cytotoxic effects caused by PS, which selectively accumulates in malignant tumor cells and is activated by light rays of the appropriate wavelength, generating singlet oxygen and free radicals, which trigger photochemical reactions in tumor cells with subsequent destruction of protein structures. Tumor tissue has a higher affinity for PSs. PSs are divided into 1st, 2nd and 3rd generation molecules. So far, 3rd generation PSs have not yet been approved for clinical use. In vitro and in vivo experimental studies confirmed the effectiveness of PDT of brain tumors using 2nd generation PSs.The simultaneous use of surgery under the control of fluorescence and PDT enables both the visualization of tumor cells and their selective destruction. Regardless of PDT, PSs are used for the purpose of auxiliary delineation of tumor borders for maximum tumor removal during fluorescence-guided surgery.The review examines the development of PDT in a historical aspect, the contribution of domestic scientists, in particular, scientists of the Institute of Neurosurgery named after acad. A. P. Romodanov, National Academy of Medical Sciences of Ukraine to the development of the problem of PDT in neuro-oncology; preclinical studies of PDT and experimental approaches to increase the efficiency of PDT are characterized. Analysis of data from clinical trials confirms that using PDT as an adjunctive treatment of malignant gliomas administered immediately after maximal resection is safe, reduces the risk of recurrence by targeting residual tumor cells in the resection cavity, improves survival and quality of life of patients. The absence of information on the development of resistance to multiple PDT sessions suggests the possibility of repeated treatments of tumor cells not removed during surgery.