title: (18)F-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.
abstract: (18)F-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(ΔEμ) 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.
authors.affiliation: Department of Pathology, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, IA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Duncan
authors.forename: T R
authors.initials: TR
authors.lastname: Rosean
authors.forename: V S
authors.initials: VS
authors.lastname: Tompkins
authors.forename: A
authors.initials: A
authors.lastname: Olivier
authors.forename: R
authors.initials: R
authors.lastname: Sompallae
authors.forename: F
authors.initials: F
authors.lastname: Zhan
authors.forename: G
authors.initials: G
authors.lastname: Tricot
authors.forename: M R
authors.initials: MR
authors.lastname: Acevedo
authors.forename: L L B
authors.initials: LL
authors.lastname: Ponto
authors.forename: S A
authors.initials: SA
authors.lastname: Walsh
authors.forename: L T
authors.initials: LT
authors.lastname: Tygrett
authors.forename: A J
authors.initials: AJ
authors.lastname: Berger
authors.forename: T
authors.initials: T
authors.lastname: Waldschmidt
authors.forename: H C
authors.initials: HC
authors.lastname: Morse
authors.forename: J J
authors.initials: JJ
authors.lastname: Sunderland
authors.forename: S
authors.initials: S
authors.lastname: Janz