title: The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts.
abstract: Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. The distribution of the apparent diffusion coefficient (ADC) exhibited an upward shift as a result of each treatment regimen. The 99-th percentile of the ADC distribution ("maximum ADC") exhibited a strong correlation with the tumour size (r2= 0.90) and with the inverse of the elastic modulus (r2= 0.96). Single-agent paclitaxel (n = 5) and combination carboplatin/paclitaxel (n = 2) treatment regimens were more effective in inducing changes in regions of higher cell density than single-agent carboplatin (n = 3) or the no-treatment control (n = 5). The maximum ADC was a good indicator of treatment-induced cell death and changes in the extracellular matrix (ECM). Comparative analysis of the tumours' ADC distribution, mechanical properties and ECM constituents provides insights into the molecular and cellular response of the ovarian tumour xenografts to chemotherapy. Increased sample sizes are recommended for future studies. We propose experimental approaches to evaluation of the timeline of the tumour's response to treatment.
authors.affiliation: Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.
authors.forename: Monique C
authors.initials: MC
authors.lastname: Tourell
authors.affiliation: Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.|Australian Prostate Cancer Research Centre - Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Ali
authors.initials: A
authors.lastname: Shokoohmand
authors.affiliation: Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.
authors.forename: Marietta
authors.initials: M
authors.lastname: Landgraf
authors.affiliation: Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.
authors.forename: Nina P
authors.initials: NP
authors.lastname: Holzapfel
authors.affiliation: Experimental Trauma Surgery, Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Patrina S P
authors.initials: PS
authors.lastname: Poh
authors.affiliation: Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Loessner
authors.affiliation: Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.
authors.forename: Konstantin I
authors.initials: KI
authors.lastname: Momot
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D016190:Carboplatin / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D038524:Diffusion Magnetic Resonance Imaging; D004359:Drug Therapy, Combination; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D016190:Carboplatin; D017239:Paclitaxel