Bailly Clément, Vidal Aurelien, Bonnemaire Coralie, Kraeber-Bodéré Françoise, Chérel Michel, Pallardy Amandine, Rousseau Caroline, Garcion Emmanuel, Lacoeuille Franck, Hindré François, Valable Samuel, Bernaudin Myriam, Bodet-Milin Caroline, Bourgeois Mickaël
Nuclear Medicine, Centre Hospitalier Universitaire (CHU) de Nantes, Nantes, France.
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.
Front Pharmacol. 2019 Jul 10;10:772. doi: 10.3389/fphar.2019.00772. eCollection 2019.
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 I, Y, Re, or Lu. 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 Bi, At, or Ac 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.
胶质母细胞瘤是最常见的成人恶性脑肿瘤,患者预后很差。尽管目前有一种积极的治疗方法——施图普方案,包括减瘤手术,随后进行放疗和化疗,但高增殖性胶质母细胞瘤的平均生存期仅为10至14个月。尽管进行了多项使用抗血管生成靶向疗法的临床试验,但在过去十年中,胶质母细胞瘤的医疗护理仍没有取得重大进展。核医学的最新进展主要得益于生物技术的进步,如放射免疫疗法、放射性肽疗法和放射性纳米颗粒,这些为胶质母细胞瘤的治疗带来了新的有前景的手段。出于治疗目的,核医学从业者通常使用β粒子发射体,如碘、钇、铼或镥。在胶质母细胞瘤领域,这些放射性同位素与纳米颗粒、单克隆抗体或肽结合。这些放射性药物化合物仅产生短暂的副作用,却使神经状态得到了稳定和/或改善。在核医学中,使用发射β粒子的同位素已成功证明了胶质母细胞瘤局部靶向内放疗的概念验证阶段。同样,铋、砹或锕等α粒子发射体似乎是一种创新且有趣的选择。事实上,α粒子在靶细胞内部或其附近释放大部分能量(与β粒子从发射点起几毫米的范围相比,α粒子在几微米范围内)。这种物理特性基于粒子与物质相互作用的差异,使得α粒子在对健康组织的辐射最小的情况下高效杀死肿瘤细胞,并能够靶向孤立的肿瘤细胞。首批临床试验证实了这一观点,并显示出良好的治疗效果和较少的副作用,从而开启了使用α疗法治疗胶质母细胞瘤医疗护理的新的有前景的时代。这篇文献综述的目的聚焦于核医学的发展领域,旨在描述与胶质母细胞瘤病理学的临床和临床前结果相关的各种参数,如靶点、载体、同位素或注射途径(全身和局部)。