期刊
BLOOD CANCER JOURNAL
卷 3, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bcj.2013.61
关键词
GEMM (genetically engineered mouse model) of human cancer; preclinical cancer drug testing; plasma cell neoplasia
资金
- Intramural Research Program of the NIAID
- NCI core Grant of The University of Iowa Holden Comprehensive Cancer Center (HCCC) [P30CA086862]
- Oberley Research Grant from HCCC
- Multiple Myeloma Research Foundation
- International Waldenstrom's Macroglobulinemia Foundation
- NCI [R01CA151354]
F-18-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 iMyc(Delta E mu) gene insertion and the widely expressed H2-L-d-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.
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