Abstract

Glioblastoma is the most common malignant adult brain tumor and has a very poor patient prognosis. The mean survival for highly proliferative glioblastoma is only 10 to 14 months despite an aggressive current therapeutic approach known as Stupp’s protocol, which consists of debulking surgery followed by radiotherapy and chemotherapy. Despite several clinical trials using anti-angiogenic targeted therapies, glioblastoma medical care remains without major progress in the last decade. Recent progress in nuclear medicine, has been mainly driven by advances in biotechnologies such as radioimmunotherapy, radiopeptide therapy, and radionanoparticles, and these bring a new promising arsenal for glioblastoma therapy. For therapeutic purposes, nuclear medicine practitioners classically use β− particle emitters like 131I, 90Y, 186/188Re, or 177Lu. In the glioblastoma field, these radioisotopes are coupled with nanoparticles, monoclonal antibodies, or peptides. These radiopharmaceutical compounds have resulted in a stabilization and/or improvement of the neurological status with only transient side effects. In nuclear medicine, the glioblastoma-localized and targeted internal radiotherapy proof-of-concept stage has been successfully demonstrated using β− emitting isotopes. Similarly, α particle emitters like 213Bi, 211At, or 225Ac appear to be an innovative and interesting alternative. Indeed, α particles deliver a high proportion of their energy inside or at close proximity to the targeted cells (within a few micrometers from the emission point versus several millimeters for β− particles). This physical property is based on particle–matter interaction differences and results in α particles being highly efficient in killing tumor cells with minimal irradiation of healthy tissues and permits targeting of isolated tumor cells. The first clinical trials confirmed this idea and showed good therapeutic efficacy and less side effects, thus opening a new and promising era for glioblastoma medical care using α therapy. The objective of this literature review is focused on the developing field of nuclear medicine and aims to describe the various parameters such as targets, vectors, isotopes, or injection route (systemic and local) in relation to the clinical and preclinical results in glioblastoma pathology.

Highlights

  • Glioblastoma is a neoplasm derived from astrocytes, a subtype of brain macroglial cells

  • The feasibility of RIT and Peptide receptor radionuclide therapy (PRRT) in glioblastoma therapy is well established, and the first clinical trial results appear to be promising with well-known targets

  • The survival rate for patients remains poor, and the standard treatment is based on debulking surgery, radiotherapy, and chemotherapy

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Summary

INTRODUCTION

Glioblastoma is a neoplasm derived from astrocytes, a subtype of brain macroglial cells. One of the first glioblastoma RIT clinical trials using a mAb directed against the EGFR antigen and radiolabeled with iodine-125 showed a significant and promising increase in median survival. In this phase II clinical study, 180 patients, of which 118 had a glioblastoma diagnosis, received intravenous or intra-arterial RIT as an adjuvant therapy after surgery, radiotherapy, and with or without chemotherapy. The radioisotope mainly used in these clinical trials is the β−/γ emitter iodine-131 This RIT protocol consists of an intracranial injection of 370 to 6,660 MBq and increased the median survival to 20.6 months for newly diagnosed glioblastomas and 14.5 months for recurrent disease (Figure 1) (Reardon et al, 2006b). Recurrence for the passive protocol was observed at 65 versus 100 days for the active targeting approach, and this appears to be the most effective therapy with the longest measured time to progression (Séhédic et al, 2017)

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