Kodaira Satoshi, Li Huizi Keiko, Konishi Teruaki, Kitamura Hisashi, Kurano Mieko, Hasegawa Sumitaka
Radiation Measurement Research Team, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
Radiation and Cancer Biology Team, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
PLoS One. 2017 Jun 28;12(6):e0178472. doi: 10.1371/journal.pone.0178472. eCollection 2017.
Recently, 211At has received increasing attention as a potential radionuclide for cancer radioimmunotherapy. It is a α-particle emitter, which is extremely effective against malignant cells. We demonstrate a method to verify the efficiency of 211At-labeled trastuzumab antibodies (211At-trastuzumab) against HER2 antigens, which has not been determined for radioimmunotherapy. A CR-39 plastic nuclear detector is used for measuring the position and the linear energy transfer (LET) of individual 211At α- particle tracks. The tracks and 211At-trastuzumab-binding cells were co-visualized by using the geometric information recorded on the CR-39. HER2-positive human gastric cancer cells (NCI-N87), labelled with 211At-trastuzumab, were dropped on the centre of the CR-39 plate. Microscope images of the cells and the corresponding α-tracks acquired by position matching were obtained. In addition, 3.5 cm × 3.5 cm macroscopic images of the whole plate were acquired. The distribution of number of α-particles emitted from single cells suggests that 80% of the 211At-trastuzumab-binding cells emitted α-particles. It also indicates that the α-particles may strike the cells several times along their path. The track-averaged LET of the α-particles is evaluated to be 131 keV/μm. These results will enable quantitative evaluation of delivered doses to target cells, and will be useful for the in vitro assessment of 211At-based radioimmunotherapeutic agents.
最近，砹-211作为一种潜在的用于癌症放射免疫治疗的放射性核素受到了越来越多的关注。它是一种α粒子发射体，对恶性细胞极为有效。我们展示了一种验证砹-211标记的曲妥珠单抗抗体（211At-曲妥珠单抗）针对HER2抗原的效率的方法，而这在放射免疫治疗中尚未得到确定。使用CR-39塑料核探测器来测量单个砹-211α粒子径迹的位置和线能量转移（LET）。通过使用记录在CR-39上的几何信息，将径迹与211At-曲妥珠单抗结合的细胞进行共可视化。用211At-曲妥珠单抗标记的HER2阳性人胃癌细胞（NCI-N87）被滴在CR-39板的中心。通过位置匹配获得细胞的显微镜图像以及相应的α径迹。此外，还获取了整个板的3.5厘米×3.5厘米宏观图像。从单个细胞发射的α粒子数量分布表明，80%的与211At-曲妥珠单抗结合的细胞发射了α粒子。这也表明α粒子在其路径上可能会多次撞击细胞。评估得出α粒子的径迹平均LET为131 keV/μm。这些结果将能够对递送至靶细胞的剂量进行定量评估，并将有助于基于砹-211的放射免疫治疗剂的体外评估。
