Document Type

Article

Peer Reviewed

1

Publication Date

11-29-2013

NLM Title Abbreviation

Blood Cancer J

Journal/Book/Conference Title

Blood Cancer Journal

DOI of Published Version

10.1038/bcj.2013.61

Abstract

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.

Keywords

OAfund, GEMM (genetically engineered mouse model) of human cancer, preclinical cancer drug testing, plasma cell neoplasia

Journal Article Version

Version of Record

Published Article/Book Citation

Blood Cancer Journal 3:11 (2013) pp. 1-12. doi:10.1038/bcj.2013.61

Rights

Copyright 2013 K. Duncan et. al.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Pathology Commons

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URL

https://ir.uiowa.edu/pathology_pubs/1