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

Stein-Martin T Fagerland; Sigrid Berg; Deborah K Hill; Sofie Snipstad; Einar Sulheim; Astrid Hyldbakk; Jana Kim; Catharina de Lange Davies

doi:10.1016/j.ultrasmedbio.2020.07.004

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

Ultrasound Med Biol. 2020 Nov;46(11):3032-3045. doi: 10.1016/j.ultrasmedbio.2020.07.004. Epub 2020 Aug 13.

Authors

Stein-Martin T Fagerland¹, Sigrid Berg², Deborah K Hill³, Sofie Snipstad⁴, Einar Sulheim⁴, Astrid Hyldbakk⁵, Jana Kim³, Catharina de Lange Davies⁶

Affiliations

¹ Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
² Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Health Research, SINTEF Digital, Trondheim, Norway; Cancer Clinic, St. Olav's Hospital, Trondheim, Norway.
³ Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olav's Hospital, Trondheim, Norway; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
⁵ Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway.
⁶ Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: catharina.davies@ntnu.no.

PMID: 32800470
DOI: 10.1016/j.ultrasmedbio.2020.07.004

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.

Keywords: Cabazitaxel; Drug delivery; Microbubbles; Nanoparticle; Prostate cancer; TRAMP model; Transgenic adenocarcinoma of the mouse prostate model; Ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / drug therapy*
Animals
Antineoplastic Agents / administration & dosage*
Disease Models, Animal
Drug Delivery Systems / methods*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microbubbles*
Prostatic Neoplasms / drug therapy*
Ultrasonic Waves*

Substances

Antineoplastic Agents