Ultrasound-Mediated Delivery of Chemotherapy into the Transgenic Adenocarcinoma of the Mouse Prostate Model
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...
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| Published in: | Ultrasound in medicine & biology Vol. 46; no. 11; pp. 3032 - 3045 |
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| Main Authors: | , , , , , , , |
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01-11-2020
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| 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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| AbstractList | 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. |
| Author | Berg, Sigrid Hyldbakk, Astrid Sulheim, Einar Kim, Jana Fagerland, Stein-Martin T. Snipstad, Sofie Davies, Catharina de Lange Hill, Deborah K. |
| Author_xml | – sequence: 1 givenname: Stein-Martin T. surname: Fagerland fullname: Fagerland, Stein-Martin T. organization: Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway – sequence: 2 givenname: Sigrid surname: Berg fullname: Berg, Sigrid organization: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway – sequence: 3 givenname: Deborah K. surname: Hill fullname: Hill, Deborah K. organization: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway – sequence: 4 givenname: Sofie surname: Snipstad fullname: Snipstad, Sofie organization: Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway – sequence: 5 givenname: Einar surname: Sulheim fullname: Sulheim, Einar organization: Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway – sequence: 6 givenname: Astrid surname: Hyldbakk fullname: Hyldbakk, Astrid organization: Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway – sequence: 7 givenname: Jana surname: Kim fullname: Kim, Jana organization: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway – sequence: 8 givenname: Catharina de Lange surname: Davies fullname: Davies, Catharina de Lange email: catharina.davies@ntnu.no organization: Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32800470$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_ultrasmedbio_2020_12_026 crossref_primary_10_1016_j_ejps_2024_106804 crossref_primary_10_1016_j_xpro_2021_100445 crossref_primary_10_1007_s13346_022_01157_y crossref_primary_10_1016_j_ultrasmedbio_2023_05_013 |
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| Issue | 11 |
| Keywords | TRAMP model Nanoparticle Transgenic adenocarcinoma of the mouse prostate model Microbubbles Drug delivery Ultrasound Prostate cancer Cabazitaxel |
| Language | English |
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