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Open AccessArticle

Tumor Drug Distribution after Local Drug Delivery by Hyperthermia, In Vivo

Center of Imaging Sciences, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Cancers 2019, 11(10), 1512; https://doi.org/10.3390/cancers11101512
Received: 9 August 2019 / Revised: 27 September 2019 / Accepted: 2 October 2019 / Published: 9 October 2019
(This article belongs to the Special Issue Hyperthermia-based Anticancer Treatments)
Tumor drug distribution and concentration are important factors for effective tumor treatment. A promising method to enhance the distribution and the concentration of the drug in the tumor is to encapsulate the drug in a temperature sensitive liposome. The aim of this study was to investigate the tumor drug distribution after treatment with various injected doses of different liposomal formulations of doxorubicin, ThermoDox (temperature sensitive liposomes) and DOXIL (non-temperature sensitive liposomes), and free doxorubicin at macroscopic and microscopic levels. Only ThermoDox treatment was combined with hyperthermia. Experiments were performed in mice bearing a human fibrosarcoma. At low and intermediate doses, the largest growth delay was obtained with ThermoDox, and at the largest dose, the largest growth delay was obtained with DOXIL. On histology, tumor areas with increased doxorubicin concentration correlated with decreased cell proliferation, and substantial variations in doxorubicin heterogeneity were observed. ThermoDox treatment resulted in higher tissue drug levels than DOXIL and free doxorubicin for the same dose. A relation with the distance to the vasculature was shown, but vessel perfusion was not always sufficient to determine doxorubicin delivery. Our results indicate that tumor drug distribution is an important factor for effective tumor treatment and that its dependence on delivery formulation merits further systemic investigation. View Full-Text
Keywords: tumor drug distribution; spatial drug distribution; temperature sensitive liposomes; hyperthermia; chemotherapy; non-temperature sensitive liposomes tumor drug distribution; spatial drug distribution; temperature sensitive liposomes; hyperthermia; chemotherapy; non-temperature sensitive liposomes
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Besse, H.C.; Barten-van Rijbroek, A.D.; van der Wurff-Jacobs, K.M.; Bos, C.; Moonen, C.T.; Deckers, R. Tumor Drug Distribution after Local Drug Delivery by Hyperthermia, In Vivo. Cancers 2019, 11, 1512.

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