Radiotoxicity after iodine-131 MIBG therapy using the micronucleus assay

本研究的目的是利用细胞动力学阻断微核试验评估I-131 Metaiodobenzylguanidine （MIBG）治疗后淋巴细胞的细胞学损伤程度。体内I-131对淋巴细胞的染色体损伤可导致微核细胞增多。方法：我们研究了18例嗜铬细胞瘤（17/18）或神经节神经瘤（1/18）患者，他们最初接受7.4 GBq的I-131-MIBG治疗。收集治疗10天后患者的分离淋巴细胞，按照Fenech和Morley的细胞分裂阻断法进行处理。在治疗后的两年内，仅从两名患者中定期获得系列血液样本。目测每500个双核细胞微核数。作为对照，也研究了治疗前同一患者的淋巴细胞。在一项体外研究中，来自8名正常志愿者的淋巴细胞暴露于0.5至2 Gy不等的剂量下，并采用相同的方法进行研究。结果：治疗后微核数（平均±SD）较对照组（46.1±7.7比9.6±2.6）显著增加（p<0.001）。在这项外照射研究中，18例患者的内辐射吸收剂量估计为1.5±0.3 Gy。注射I-131-MIBG后的微核频率在两年内逐渐下降到接近基线（即治疗前）水平。结论：体内I-131-MIBG诱导的淋巴细胞微核频率相对较低，治疗后淋巴细胞微核频率增加，支持了7.4 GBq I-131-MIBG治疗嗜铬细胞瘤或神经节神经瘤患者短期非随机损伤有限且可逆的观点。

The purpose of the present study was to evaluate the degree of cytological radiation damage to lymphocytes after I-131 Metaiodobenzylguanidine (MIBG) therapy using the cytokinesis-blocked micronucleus assay. The chromosomal damage to lymphocytes induced by I-131 in vivo should result in augmentation of the cells with micronuclei.Methods: We studied 18 patients with pheochromocytoma (17/18) or ganglioneuroma (1/18), who were treated initially with 7.4 GBq of I-131-MIBG. Isolated lymphocytes collected from patients 10 days after the therapy were harvested and treated according to the cytokinesis-blocked method of Fenech and Morley. Serial blood samples were obtained periodically only from two patients for two years after therapy. Micronucleus number of micronulei per 500 binucleated cells was scored by visual inspection. As controls, lymphocytes from the same patients before the therapy were also studied. In an in vitro study, lymphocytes from eight normal volunteers were exposed to doses varying from 0.5 to 2 Gy and studied with the same method.Results: The mean number (mean±SD) of micronuclei after treatment was significantly increased (p<0.001) as compared to control subjects (46.1±7.7 vs. 9.6±2.6). Internal radiation absorbed doses estimated for 18 patients were 1.5±0.3 Gy in this external irradiation study. The frequency of micronuclei post-administration of I-131-MIBG gradually decreased to near baseline (ie pre-therapy) levels by two years.Conclusions: The relatively low frequency of lymphocyte micronuclei induced by I-131-MIBG in vivo and recovery of increasing frequency of lymphocyte micronuclei after therapy supported the contention that short-term non-stochastic damage of this therapy with 7.4 GBq of I-131-MIBG in pheochromocytoma or ganglioneuroma patients is limited and reversible.