Ex Vivo Activity Quantification in Micrometastases at the Cellular Scale Using the α-Camera Technique
Ex Vivo Activity Quantification in Micrometastases at the Cellular Scale Using the α-Camera Technique
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DOI：
10.2967/jnumed.112.113001
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发表时间：
2013-08-01
影响因子：
9.3
通讯作者：
Back, Tom
中科院分区：
文献类型：
--
作者：
Chouin, Nicolas;Lindegren, Sture;Back, Tom
靶向α治疗（达特）似乎是消除恶性循环、微小残留或微转移细胞的理想治疗技术。这些类型的恶性肿瘤通常是临床下的，使潜在治疗的评估复杂化。本研究提出了一种用a-相机装置进行离体活性定量的方法，允许测量几十微米生物结构中肿瘤细胞所吸收的活性。方法：我们研究了从卵巢癌小鼠模型注射后的达特放射免疫标记物标记的TAT-211的微转移。在不同的时间点，切除生物样品并冷冻切片。通过2个相邻切片的组合信息确定肿瘤细胞的活性水平和数量：一个暴露于α照相机，另一个用苏木精和伊红染色。对于2种不同的注射活性（6和1 MBq），推导出包含少于10个细胞的肿瘤细胞簇的时间-活性曲线。结果：放射免疫偶联物在肿瘤细胞表面有较高的摄取和良好的滞留。基于测量的时间积分活性的剂量计算表明，对于1 MBq的注射活性，分离的肿瘤细胞接受至少12戈伊。在较大的微转移中（
Targeted alpha-therapy (TAT) appears to be an ideal therapeutic technique for eliminating malignant circulating, minimal residual, or micrometastatic cells. These types of malignancies are typically infraclinical, complicating the evaluation of potential treatments. This study presents a method of ex vivo activity quantification with an a-camera device, allowing measurement of the activity taken up by tumor cells in biologic structures a few tens of microns. Methods: We examined micrometastases from a murine model of ovarian carcinoma after injection of a radioimmunoconjugate labeled with At-211 for TAT. At different time points, biologic samples were excised and cryosectioned. The activity level and the number of tumor cells were determined by combined information from 2 adjacent sections: one exposed to the alpha-camera and the other stained with hematoxylin and eosin. The time-activity curves for tumor cell clusters, comprising fewer than 10 cells, were derived for 2 different injected activities (6 and 1 MBq). Results: High uptake and good retention of the radioimmunoconjugate were observed at the surface of tumor cells. Dosimetric calculations based on the measured time-integrated activity indicated that for an injected activity of 1 MBq, isolated tumor cells received at least 12 Gy. In larger micrometastases (