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

• Published in: Ultrasound in medicine & biology Vol. 46; no. 11; pp. 3032 - 3045
• Main Authors: Fagerland, Stein-Martin T., Berg, Sigrid, Hill, Deborah K., Snipstad, Sofie, Sulheim, Einar, Hyldbakk, Astrid, Kim, Jana, Davies, Catharina de Lange
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-11-2020
• Subjects: Cabazitaxel; Drug delivery; Microbubbles; Nanoparticle; Prostate cancer; TRAMP model; Transgenic adenocarcinoma of the mouse prostate model; Ultrasound; TRAMP model; Nanoparticle; Transgenic adenocarcinoma of the mouse prostate model; Microbubbles; Drug delivery; Ultrasound; Prostate cancer; Cabazitaxel
• ISSN: 0301-5629; 1879-291X
• DOI: 10.1016/j.ultrasmedbio.2020.07.004

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.