• Radioimmunotherapy application in Glioblastoma multiforme Treatment
  • Mohammad Farhadi Rad,1,* Hossein Azadinejad,2 Mahmood Mohammadi Sadr,3 Mohammad Ghaderian,4 Mahboobeh soleimanpoor,5
    1. Department of Radiology and nuclear medicine, School of paramedical, Kermanshah University of Medical Sciences, Kermanshah, Iran
    2. Department of immunology, school of medicine, Kermanshah university of medical sciences , Kermanshah, Iran
    3. Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
    4. Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
    5. Department of Radiology Technology, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


  • Introduction: The incidence of brain tumors is increasing slightly each year and patient prognosis remains disappointing. The lower Karnofsky performance score and older age are associated with poorer prognosis. Standard therapy for the management of brain tumors in routine clinical practice consists of debulking surgery, radiation therapy, and chemotherapy. Therefore, researchers are looking for ways to improve the therapeutic index as an important therapeutic goal. Gliomas, cancer cells derived from glial progenitor cells, account for approximately 75% of all adult primary malignant brain tumors (about 30% of all brain tumors) and are characterized by poor outcomes. In children, primary brain tumors are the second leading cause of cancer death after leukemia and the most common solid tumor. Glioblastoma multiforme (GBM) is a rapidly growing glioma that arises from astrocytes and oligodendrocytes. GBM often referred to as grade IV glioma, is the most lethal primary brain tumor. The standard treatment of GBM consisting neurosurgery, followed by radiotherapy. Nonetheless because of its invasive and aggressive growth pattern GBM cannot be completely controlled. To improve local tumor control, considerable research was implemented into new GBM therapies, one of the promising techniques being radioimmunotherapy (RIT). RIT is a nuclear medicine modality that uses a radionuclide component combined with a monoclonal antibody(mAb) which is targeted against surface tumor antigens or antigens in the tumor microenvironment. This approach has the advantages of selective delivery of antibodies and cell-killing characteristics of radionuclides. RIT is based on the presence of specific antigens within the tumor that are able to bind with MAbs after local or systemic administration. For a successful RIT, it is essential to select surface antigen present on the majority of tumor cells and of a specific targeting antibody. Furthermore, this surface antigen should have a low expression (ideally no expression) on normal cells. Targets and Radionuclides that have shown potential results in radioimmunotherapy of GBM are going to be discussed in this paper.
  • Methods: To conduct this article we searched Scopus, PubMed, and google scholar databases in the period from 2018 to 2022 using "Radioimmunotherapy", "Glioblastoma multiforme", "Glioma" and "Radionuclide" keywords. Duplicated titles were removed by endnote software and after checking abstracts related articles were reviewed.
  • Results: Epidermal growth factor receptor (EGFR) and tenascin are targets that have shown therapeutic potential in literature and for brain disorders. Furthermore, some preclinical and clinical trials were implemented with promising results. EGFR expression has been identified in 19-85% of primary malignant gliomas, especially in GBM. However, its expression is low in normal brain tissue. Probably the most investigated target for brain tumors is Tenascin, which is expressed all over the extracellular matrix of gliomas. There are other molecular targets that have shown promising results to treat tumors like the extra domain B of fibronectin (EDB), human neural cell adhesion molecule (NCAM) and disialoganglioside GD2. Solid tumors like GBM can be treated with radionuclides that emit α and β –particles. More than 95 percent of clinical trials have used 131I and 90Y as a standard to which all other radionuclides are compared. Availability, favorable emission properties, and flexible radiochemistry have led to the use of these β-particle-emitting radionuclides in RIT. The treatment of GBM α- and β-emitting radionuclides have some advantages and disadvantages because of their radiobiological and physical characteristics. Half-life, range in tissue, mean energy, and linear energy transfer (LET) are important parameters that can affect targeted cells. Furthermore, effective half-life which can match the properties of the tumor when choosing a suitable radionuclide for clinical use is a highly valued parameter in the context of RIT.
  • Conclusion: Despite advances in surgery radiotherapy and chemotherapy approaches GBM relative survival is below 7% within 5 years. RIT has proven successful in clinical results in hematological malignancies. However, because of several reasons which are mostly related to the different biological properties of solid tumors and hematological cancers, RIT has not indicated significant success in solid tumors. Numerous powerful tools for GBM therapy have been provided by recent advances in nuclear medicine and biotechnological technologies that are related to molecular knowledge and new clinical opportunities have been created by the development of innovative radionuclides. Furthermore, A better understanding of the tumoral microenvironment and radionuclides properties is needed to optimize GBM treatment using RIT approaches.
  • Keywords: Radioimmunotherapy, Glioblastoma multiforme, Glioma, and Radionuclide