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Old 06-15-2018, 09:32 AM   #1
Lani
Senior Member
 
Join Date: Mar 2006
Posts: 4,778
Thumbs up ffor those with lepto-meningeal metastases

Sci Rep. 2018 Jun 13;8(1):9013. doi: 10.1038/s41598-018-27335-y.
Preliminary Investigation of Focused Ultrasound-Facilitated Drug Delivery for the Treatment of Leptomeningeal Metastases.

O'Reilly MA1,2, Chinnery T3, Yee ML3, Wu SK3,4, Hynynen K3,4,5, Kerbel RS4,6, Czarnota GJ3,4,7,8, Pritchard KI9,10,11, Sahgal A3,7,8.
Author information
1
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada. moreilly@sri.utoronto.ca.
2
Department of Medical Biophysics, University of Toronto, Toronto, Canada. moreilly@sri.utoronto.ca.
3
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
4
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
5
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
6
Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
7
Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.
8
Department of Radiation Oncology, University of Toronto, Toronto, Canada.
9
Evaluative Clinical Sciences, Sunnybrook Health Sciences Centre, Toronto, Canada.
10
Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.
11
Department of Medicine, University of Toronto, Toronto, Canada.
Abstract
Leptomeningeal metastases (LM) are a serious complication of cancer in the central nervous system (CNS) and are diagnosed in approximately 5% of patients with solid tumors. Effective treatment using systemically administered therapeutics is hindered by the barriers of the CNS. Ultrasound can mediate delivery of drugs through these barriers. The goal of this study was to test the feasibility of using ultrasound-mediated drug delivery to improve the treatment of LM. LM was induced in the spinal cord of athymic rats by injecting HER2-expressing breast cancer cells into the subarachnoid space of the thoracic spine. Animals were divided into three groups: no treatment (n = 5), trastuzumab only (n = 6) or trastuzumab + focused ultrasound + microbubbles (FUS + MBs) (n = 7). Animals in groups 2 and 3 were treated weekly with intravenous trastuzumab +/- FUS + MBs for three weeks. Suppression in tumor growth was qualitatively observed by MRI in the group receiving ultrasound, and was confirmed by a significant difference in the tumor volume measured from the histology data (25 ± 17 mm3 vs 8 ± 5 mm3, p = 0.04 in the trastuzumab-only vs trastuzumab + FUS + MBs). This pilot study demonstrates the potential of ultrasound-mediated drug delivery as a novel treatment for LM. Future studies will extend this work to larger cohorts and the investigation of LM arising from other cancers.
PMID: 29899537 DOI: 10.1038/s41598-018-27335-y
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