Kinuya Seigo, Li Xiao-Feng, Yokoyama Kunihiko, Mori Hirofumi, Shiba Kazuhiro, Watanabe Naoto, Shuke Noriyuki, Bunko Hisashi, Michigishi Takatoshi, Tonami Norihisa
Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 920-8640 Kanazawa, Ishikawa, Japan.
Eur J Nucl Med Mol Imaging. 2003 Sep;30(9):1246-50. doi: 10.1007/s00259-003-1214-1. Epub 2003 Jun 17.
Internal radiotherapy involving systemic administration of iodine-131 metaiodobenzylguanidine ((131)I-MIBG) in neural crest tumours such as neuroblastoma has shown considerable success. Although peritoneal seeding of neuroblastoma occurs less often than metastases to organs such as the liver, no effective treatments exist in this clinical setting. Previous reports have demonstrated the effectiveness of peritoneal application of chemotherapeutic drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas. Local delivery of (131)I-MIBG should produce more favourable dosimetry in comparison with its systemic administration in the treatment of peritoneal neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma cells. Two weeks after cell inoculation, comparative biodistribution studies were performed following i.v. or i.p. administration of (131)I-MIBG. Mice were treated with 55.5 MBq of (131)I-MIBG administered either i.v. or i.p. at 2 weeks. Intraperitoneal injection of (131)I-MIBG produced significantly higher tumour accumulation than did i.v. injection ( P<0.01). Therapeutic ratios of i.p. injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy with i.v. administered (131)I-MIBG failed to improve the survival of mice; mean survival of untreated mice and mice treated with i.v. administration of (131)I-MIBG was 59.3+/-3.9 days and 60.6+/-2.8 days, respectively. On the other hand, radiotherapy delivered via i.p. administration of (131)I-MIBG prolonged survival of mice to 94.7+/-17.5 days ( P<0.02 vs untreated controls and mice treated with i.v. (131)I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of (131)I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with i.v. injection. These results indicate the benefits of locoregional delivery of (131)I-MIBG in the treatment of peritoneal neuroblastoma.
涉及全身给予碘 - 131间碘苄胍((131)I - MIBG)的内照射放疗在神经母细胞瘤等神经嵴肿瘤治疗中已取得显著成效。尽管神经母细胞瘤的腹膜种植比转移至肝脏等器官的情况少见,但在这种临床情况下尚无有效的治疗方法。既往报道已证实腹膜应用化疗药物或放射性标记单克隆抗体在几种癌症治疗中的有效性。与全身给药相比,局部给予(131)I - MIBG在治疗腹膜神经母细胞瘤时应能产生更有利的剂量分布。在当前研究中,通过腹腔注射SK - N - SH神经母细胞瘤细胞在Balb/c nu/nu小鼠中建立了腹膜神经母细胞瘤模型。细胞接种两周后,在静脉注射或腹腔注射(131)I - MIBG后进行了比较生物分布研究。在第2周时,给小鼠静脉注射或腹腔注射55.5 MBq的(131)I - MIBG进行治疗。腹腔注射(131)I - MIBG产生的肿瘤摄取量显著高于静脉注射(P <0.01)。腹腔注射的治疗比是静脉注射的4至14倍。静脉注射(131)I - MIBG进行放疗未能提高小鼠的生存率;未治疗小鼠和静脉注射(131)I - MIBG治疗小鼠的平均生存时间分别为59.3±3.9天和60.6±2.8天。另一方面,通过腹腔注射(131)I - MIBG进行放疗使小鼠的生存时间延长至94.7±17.5天(与未治疗对照组和静脉注射(131)I - MIBG治疗的小鼠相比,P <0.02)。估计腹腔注射55.5 MBq的(131)I - MIBG时肿瘤吸收的辐射剂量为4140 cGy,静脉注射时为450 cGy。这些结果表明局部给予(131)I - MIBG在治疗腹膜神经母细胞瘤方面的益处。