Radiology Section, Department of Medical Diagnostic Sciences, Biomedical Sciences Group, University of Leuven, Leuven, Belgium.
Invest New Drugs. 2012 Oct;30(5):2050-65. doi: 10.1007/s10637-011-9758-6. Epub 2011 Oct 18.
Cancer is one of the major causes of death for non-transmissible chronic diseases worldwide. Conventional treatments including surgery, chemotherapy and external beam radiotherapy are generally far from curative. Complementary therapies are attempted for achieving more successful treatment response. Systemic targeted radiotherapy (STR) is a radiotherapeutic modality based on systemic administration of radioactive agents for selectively delivering high doses of energy to destroy cancer cells. For this purpose, diverse tumour-target specific agents including monoclonal antibodies (MoAb), MoAb fragments and peptides have been tested and some of them have already got FDA approval for clinical use. However, MoAbs and their tailored analogues have shown non-homogeneous tumour distribution, limited diffusion, insufficient intratumoral accumulation and retention, unwanted uptake in normal tissues and scarcity of identified cancer antigens for generating new MoAbs. Similarly, peptides have also exhibited retention in normal organs, lacks of favourable membrane permeability or drug cell internalization and short-term residence in cancer cells. Recently, a new category of target-specific agent with strong affinity for necrosis has emerged as an excellent option for developing targeted radiotherapeutic agents to be used after necrosis-inducing treatments (NITs). The combination of their high, specific and long-term accumulation and retention at necrotic sites with the crossfire effect of ionizing particle-emitters allows irradiating adjacent residual viable tumour cells during a prolonged period of time. It may considerably enhance the therapeutic response and open a new horizon for improved cancer treatability or curability.
癌症是全球非传染性慢性疾病死亡的主要原因之一。包括手术、化疗和外照射放疗在内的常规治疗方法通常远非治愈性的。人们尝试采用补充疗法来实现更成功的治疗反应。全身靶向放疗（STR）是一种基于全身给予放射性药物的放射治疗方式，旨在选择性地将高剂量能量传递到癌细胞中以破坏它们。为此，人们测试了各种肿瘤靶向特异性药物，包括单克隆抗体（MoAb）、MoAb 片段和肽，其中一些已经获得 FDA 批准用于临床应用。然而，MoAbs 及其定制类似物表现出不均匀的肿瘤分布、有限的扩散、不足以在肿瘤内积累和保留、在正常组织中不必要的摄取以及缺乏可识别的癌症抗原来产生新的 MoAbs。同样，肽也表现出在正常器官中的保留、缺乏有利的膜通透性或药物细胞内化以及在癌细胞中的短期停留。最近，出现了一类新的具有强烈坏死亲和力的靶向特异性药物，成为开发用于坏死诱导治疗（NITs）后使用的靶向放射治疗药物的绝佳选择。它们在坏死部位的高特异性和长期积累和保留与电离粒子发射体的交火效应相结合，使得可以在较长时间内辐照相邻的残留存活肿瘤细胞。这可能会极大地增强治疗反应，并为改善癌症可治疗性或治愈率开辟新的前景。
