title: Molecular Imaging of Tumors Using a Quantitative T 1 Mapping Technique via Magnetic Resonance Imaging.
abstract: Magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM) with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T 1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA)3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T 1-weighted imaging techniques. In this study, we used a dynamic quantitative T 1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA)3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA)3 agent, a scrambled-Tris-(Gd-DOTA)3 control agent, and the non-specific clinical contrast agent Optimark(™) all enhanced flank tumors of human glioma cells with similar maximal changes on T 1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T 1 while the specific agent SBK2-Tris-(Gd-DOTA)3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T 1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T 1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA)3 agent over time compared to the non-specific contrast agent currently in clinical use.
authors.affiliation: Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Mette L
authors.initials: ML
authors.lastname: Johansen
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Sonya E
authors.initials: SE
authors.lastname: Craig
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Vincent
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Radiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Radiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Erokwu
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Agnes
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pokorski
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Radiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA ; The National Foundation for Cancer Research (NFCR) Center for Molecular Imaging, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: James
authors.initials: J
authors.lastname: Basilion
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Radiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Urology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Gulani
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Radiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Griswold
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Radiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Flask
authors.affiliation: Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA ; Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
keywords: PTPmu; T1 relaxation time; cancer imaging; magnetic resonance imaging; molecular imaging; protein tyrosine phosphatase; tumor detection