title: Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids.
abstract: Inflammation plays a prominent role in tumor growth. Anti-inflammatory drugs have therefore been proposed as anti-cancer therapeutics. In this study, we determined the anti-angiogenic activity of a single dose of liposomal prednisolone phosphate (PLP-L), by monitoring tumor vascular function and viability over a period of one week. C57BL/6 mice were inoculated subcutaneously with B16F10 melanoma cells. Six animals were PLP-L-treated and six served as control. Tumor tissue and vascular function were probed using MRI before and at three timepoints after treatment. DCE-MRI was used to determine K(trans), v(e), time-to-peak, initial slope and the fraction of non-enhancing pixels, complemented with immunohistochemistry. The apparent diffusion coefficient (ADC), T(2) and tumor size were assessed with MRI as well. PLP-L treatment resulted in smaller tumors and caused a significant drop in K(trans) 48 h post-treatment, which was maintained until one week after drug administration. However, this effect was not sufficient to significantly distinguish treated from non-treated animals. The therapy did not affect tumor tissue viability but did prevent the ADC decrease observed in the control group. No evidence for PLP-L-induced tumor vessel normalization was found on histology. Treatment with PLP-L altered tumor vascular function. This effect did not fully explain the tumor growth inhibition, suggesting a broader spectrum of PLP-L activities.
authors.affiliation: Department of Biomedical Engineering, Biomedical NMR, Eindhoven University of Technology, 2.03b N-laag, PO Box 513, 5600 MB, Eindhoven, The Netherlands. E.Kluza@tue.nl
authors.forename: Ewelina
authors.initials: E
authors.lastname: Kluza
authors.forename: Marieke
authors.initials: M
authors.lastname: Heisen
authors.forename: Sophie
authors.initials: S
authors.lastname: Schmid
authors.forename: Daisy W J
authors.initials: DW
authors.lastname: van der Schaft
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Schiffelers
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Bart M
authors.initials: BM
authors.lastname: ter Haar Romeny
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D005938:Glucocorticoids; D008081:Liposomes; C009022:prednisolone phosphate; D011239:Prednisolone