title: Multimodal assessment of early tumor response to chemotherapy: comparison between diffusion-weighted MRI, 1H-MR spectroscopy of choline and USPIO particles targeted at cell death.
abstract: The aim of this study was to determine the value of different magnetic resonance (MR) protocols to assess early tumor response to chemotherapy. We used a murine tumor model (TLT) presenting different degrees of response to three different cytotoxic agents. As shown in survival curves, cyclophosphamide (CP) was the most efficient drug followed by 5-fluorouracil (5-FU), whereas the etoposide treatment had little impact on TLT tumors. Three different MR protocols were used at 9.4 Tesla 24 h post-treatment: diffusion-weighted (DW)-MRI, choline measurement by (1) H MRS, and contrast-enhanced MRI using ultrasmall iron oxide nanoparticles (USPIO) targeted at phosphatidylserine. Accumulation of contrast agent in apoptotic tumors was monitored by T(2) -weighted images and quantified by EPR spectroscopy. Necrosis and apoptosis were assessed by histology. Large variations were observed in the measurement of choline peak areas and could not be directly correlated to tumor response. Although the targeted USPIO particles were able to significantly differentiate between the efficiency of each cytotoxic agent and best correlated with survival endpoint, they present the main disadvantage of non-specific tumor accumulation, which could be problematic when transferring the method to the clinic. DW-MRI presents a better compromise by combining longitudinal studies with a high dynamic range; however, DW-MRI was unable to show any significant effect for 5-FU. This study illustrates the need for multimodal imaging in assessing tumor response to treatment to compensate for individual limitations.
authors.affiliation: Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: K A
authors.initials: KA
authors.lastname: Radermacher
authors.forename: J
authors.initials: J
authors.lastname: Magat
authors.forename: C
authors.initials: C
authors.lastname: Bouzin
authors.forename: S
authors.initials: S
authors.lastname: Laurent
authors.forename: T
authors.initials: T
authors.lastname: Dresselaers
authors.forename: U
authors.initials: U
authors.lastname: Himmelreich
authors.forename: S
authors.initials: S
authors.lastname: Boutry
authors.forename: I
authors.initials: I
authors.lastname: Mahieu
authors.forename: L
authors.initials: L
authors.lastname: Vander Elst
authors.forename: O
authors.initials: O
authors.lastname: Feron
authors.forename: R N
authors.initials: RN
authors.lastname: Muller
authors.forename: B F
authors.initials: BF
authors.lastname: Jordan
authors.forename: B
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D002794:Choline / Q000032:analysis*; D003911:Dextrans; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D011522:Protons; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003911:Dextrans; D058185:Magnetite Nanoparticles; D011522:Protons; C097921:ferumoxtran-10; D002794:Choline