Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids

E. Kluza, M. Heisen, S. Schmid, D.W. van der Schaft, R.M. Schiffelers, G. Storm, B.M. ter Haar Romeny, G.J. Strijkers, K. Nicolay

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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.
Original languageEnglish
Pages (from-to)143-153
JournalAngiogenesis
Volume14
Issue number2
DOIs
Publication statusPublished - 1 Jan 2011

Cite this

Kluza, E., Heisen, M., Schmid, S., van der Schaft, D. W., Schiffelers, R. M., Storm, G., ter Haar Romeny, B. M., Strijkers, G. J., & Nicolay, K. (2011). Multi-parametric assessment of the anti-angiogenic effects of liposomal glucocorticoids. Angiogenesis, 14(2), 143-153. https://doi.org/10.1007/s10456-010-9198-5