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Ultrasound-Mediated Delivery of Chemotherapy into the Transgenic Adenocarcinoma of the Mouse Prostate Model

Abstract

Ultrasound (US) in combination with microbubbles (MB) has had promising results in improving delivery of chemotherapeutic agents. However, most studies are done in immunodeficient mice with xenografted tumors. We used two phenotypes of the spontaneous transgenic adenocarcinoma of the mouse prostate (TRAMP) model to evaluate if US + MB could enhance the therapeutic efficacy of cabazitaxel (Cab). Cab was either injected intravenously as free drug or encapsulated into nanoparticles. In both cases, Cab transiently reduced tumor and prostate volume in the TRAMP model. No additional therapeutic efficacy was observed combining Cab with US + MB, except for one tumor. Additionally, histology grading and immunostaining of Ki67 did not reveal differences between treatment groups. Mass spectrometry revealed that nanoparticle encapsulation of Cab increased the circulation time and enhanced the accumulation in liver and spleen compared with free Cab. The therapeutic results in this spontaneous, clinically relevant tumor model differ from the improved therapeutic response observed in xenografts combining US + MB and chemotherapy.

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Category

Academic article

Language

English

Author(s)

  • Stein-Martin Tilrum Fagerland
  • Sigrid Berg
  • Deborah Katherine Hill
  • Sofie Snipstad
  • Einar Sulheim
  • Astrid Hyldbakk
  • Jana Kim
  • Catharina de Lange Davies

Affiliation

  • SINTEF Industry / Biotechnology and Nanomedicine
  • SINTEF Digital / Health Research
  • St. Olavs Hospital, Trondheim University Hospital
  • Norwegian University of Science and Technology

Year

2020

Published in

Ultrasound in Medicine and Biology

ISSN

0301-5629

Volume

46

Issue

11

Page(s)

3032 - 3045

View this publication at Norwegian Research Information Repository