99mTc-HYNIC-annexinⅤ活体检测单次放疗后肿瘤细胞凋亡

摘要

Objective:The aims of this study are to detect the apoptosis of cancer cells after a single dose of radiotherapy with 99mTc-HYNIC-annexin V and to investigate the correlation among early apoptosis, radio-therapeutic dose, and radio-sensitivity. Methods:Ten days after respective inoculations of EL4 lymphoma and S180 sarcoma in their right upper limbs, the mice were randomly divided into imaging group (Group One) and observation group (Group Two). In Group One, 99mTc-HYNIC-annexin V was injected via the caudal vein after different doses of irradiation. Approximately 2 h later, clinical imaging was conducted by single-photon emission-computed tomography. The mice were sacrificed to evaluate the bio-distribution of 99mTc in each specimen. Cell count during apoptosis was conducted through the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Observation was conducted in Group Two for 2 weeks after the irradiation. Results:Tumor uptake of 99mTc-HYNIC-annexin V significantly correlated with the number of TUNEL-positive cells, which concordantly increased with the increase of dosage (r=0.892, P=0.000). With the same dose (0 or 8 Gy), the values of%ID/g, T/B, T/M, and TUNEL-positive cell number of EL4 lymphoma were significantly higher compared with those of S180 sarcoma. EL4 lymphoma was entirely minimized after irradiation at 8 Gy. Conclusion: 99mTc-HYNIC-annexin V can detect early apoptosis in vivo in tumors receiving radiation. The irradiation-induced apoptosis in vivo determined with 99mTc-HYNIC-annexin V positively correlates with the curative effect of tumors. The detection of tumor cell apoptosis via 99mTc-HYNIC-annexin V helps estimate radio-sensitivity, and can become a predictive index for radiotherapy.%　　目的：本研究旨在采用99mTc-HYNIC-annexinⅤ活体检测放疗后肿瘤的凋亡情况，并初步探讨凋亡与照射剂量及肿瘤敏感性的关系。方法：将EL4淋巴瘤和S180肉瘤细胞株分别接种于实验小鼠右腋下10 d，随机分成显像组和观察组。显像组不同剂量照射后尾静脉注射99mTc-HYNIC-annexinⅤ，2 h后SPECT显像，取组织称重后分别测量放射性计数，计算每克组织百分注射剂量率（%ID/g）及T/B、T/M放射性比值，应用TUNEL法检测肿瘤凋亡细胞数。观察组照射后观察2周。结果：EL4淋巴瘤随照射剂量增加显影逐渐清晰，凋亡细胞数增多，且与%ID/g呈正相关（r=0.892，P<0.001）；S180肉瘤不明显。相同剂量（0 Gy或8 Gy）照射，EL4淋巴瘤放射性分布及凋亡细胞数明显高于S180肉瘤。8 Gy照射后，S180肉瘤仅缩小0.1 cm，EL4淋巴瘤完全消退。结论：99mTc-HYNIC-annexinⅤ可早期活体检测放疗诱导的肿瘤凋亡。放射诱导的凋亡与疗效呈正相关，检测凋亡有助于判断其对放疗的敏感性，可以作为预后的指标。