Radiotoxicity after iodine-131 MIBG therapy using the micronucleus assay

本研究的目的是使用细胞质分裂阻断微核试验评估I-131间碘苄胍（MIBG）治疗后淋巴细胞的细胞学辐射损伤程度。方法：对18例嗜铬细胞瘤（17/18）和神经节细胞瘤（1/18）患者进行了I-131-MIBG（7.4GBq）治疗。从治疗后10天的患者收集分离的淋巴细胞，并根据Fenech和莫利的分裂阻断方法进行处理。在治疗后的两年内，仅从两名患者定期获得系列血液样本。通过目视检查对每500个双核细胞的微核数进行评分。作为对照，还研究了治疗前来自相同患者的淋巴细胞。在体外研究中，用相同的方法对8名正常志愿者的淋巴细胞进行了0.5 ~ 2戈伊剂量照射的研究，结果：与对照组（46.1±7.7 vs.9.6 ±2.6）相比，照射后微核的平均数（mean±SD）显著增加（p<0.001）。外照射研究中18例患者的内照射吸收剂量估计为1.5±0.3戈伊。I-131-MIBG给药后微核频率逐渐降低至接近基线（即治疗前）水平下降了两年。I-131-MIBG在体内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恢复，这支持了7.4 GBq I-131-MIBG治疗的短期非随机损伤的论点。MIBG在嗜铬细胞瘤或神经节细胞瘤患者中是有限的和可逆的。

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.