文章：

¹⁸F-FDG-PET/CT成像用于IL-6和MYC驱动的人类多发性骨髓瘤小鼠模型，可客观评估浆细胞肿瘤进展及对蛋白酶体抑制剂ixazomib的治疗反应

¹⁸F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib

原文发布日期：2013-11-29

DOI: 10.1038/bcj.2013.61

类型: Original Article

开放获取: 是

英文摘要：

¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are useful imaging modalities for evaluating tumor progression and treatment responses in genetically engineered mouse models of solid human cancers, but the potential of integrated FDG-PET/CT for assessing tumor development and new interventions in transgenic mouse models of human blood cancers such as multiple myeloma (MM) has not been demonstrated. Here we use BALB/c mice that contain the newly developed iMycΔEμ gene insertion and the widely expressed H2-Ld-IL6 transgene to demonstrate that FDG-PET/CT affords an excellent research tool for assessing interleukin-6- and MYC-driven plasma cell tumor (PCT) development in a serial, reproducible and stage- and lesion-specific manner. We also show that FDG-PET/CT permits determination of objective drug responses in PCT-bearing mice treated with the investigational proteasome inhibitor ixazomib (MLN2238), the biologically active form of ixazomib citrate (MLN9708), that is currently in phase 3 clinical trials in MM. Overall survival of 5 of 6 ixazomib-treated mice doubled compared with mice left untreated. One outlier mouse presented with primary refractory disease. Our findings demonstrate the utility of FDG-PET/CT for preclinical MM research and suggest that this method will play an important role in the design and testing of new approaches to treat myeloma.

摘要翻译： 

¹⁸F-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）与计算机断层扫描（CT）是评估实体人类癌症基因工程小鼠模型中肿瘤进展和治疗反应的有效成像方式，但整合性FDG-PET/CT在人类血液癌症（如多发性骨髓瘤）转基因小鼠模型中评估肿瘤发展及新干预措施的潜力尚未得到证实。本研究通过携带新开发的iMycΔEμ基因插入和广泛表达的H2-Ld-IL6转基因的BALB/c小鼠证明，FDG-PET/CT可为评估白细胞介素-6与MYC驱动的浆细胞瘤发展提供连续、可重复且具有分期与病灶特异性的优质研究工具。我们还发现，FDG-PET/CT能够客观测定携带浆细胞瘤的小鼠使用实验性蛋白酶体抑制剂伊沙佐米（MLN2238）——即枸橼酸伊沙佐米（MLN9708）的生物活性形式——治疗后的药物反应，该药物目前正处于多发性骨髓瘤的III期临床试验阶段。与未治疗组相比，6只伊沙佐米治疗组小鼠中有5只的总生存期实现翻倍，仅1例小鼠出现原发难治性疾病。我们的研究结果证实了FDG-PET/CT在多发性骨髓瘤临床前研究中的实用价值，并提示该方法在骨髓瘤新治疗方案的设计与测试中将发挥重要作用。

原文链接：

¹⁸F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib