# Translational use of focused ultrasound to increase blood-tumor barrier permeability as a mechanism to increase drug accumulation into brain metastases of breast cancer

> **NIH NIH F99** · WEST VIRGINIA UNIVERSITY · 2022 · $42,243

## Abstract

Project Summary: Once a cancer has disseminated approximately 20% of the time it will go to
brain. The most common brain metastases originate from lung, breast and or skin. Brain
metastases often are often not diagnosed until neurological symptoms are pronounced, which
usually indicates a significant disease burden. Traditional therapy including surgical resection
and radiation therapy have a low degree of efficacy as evidenced by a low two-year survival of
8.1%. The blood-tumor barrier (BTB) while disrupted compared to the blood-brain barrier,
remains a physicochemical barrier limiting effective drug accumulation in 90% of lesions. Our
long-term goal is to temporarily disrupt the BTB and enhance drug accumulation within
metastatic brain lesions. We hypothesize that disruption of the BTB will allow drugs to
accumulate at cytotoxic concentrations within the lesions, increasing chemotherapeutic efficacy
and prolonging overall survival. Transcranial low intensity focused ultrasound (LiFUS) has been
previously used in neurological disorders to non-invasively increase drug accumulation within
the brain using increased paracellular transport between endothelial cells. In this study, we
propose the investigation of LiFUS exposure on BTB permeability of standard chemotherapies
in order to increase tumor cytotoxicity and survival in mice. To do this, we first need to control
LiFUS mediated BTB disruption. The first specific aim will elucidate key LiFUS parameters
including cavitation dose, power and duration on BTB permeability as well as brain/lesion
accumulation of chemotherapeutics. Survival and tumor progression will also be measured
using this model, with weekly treatments being completed. The second specific aim will
elucidate potential long-term vascular changes induced by the ultrasound waves. Specifically,
we will evaluate five proteins that are integral to the BTB, over five time points (24h – 7d), with
two doses cavitation doses in naive and treated animals. Two efflux transporters (P-gp, BCRP)
will be evaluated for expression and the ability to efflux substrates. Three tight junction proteins
will be evaluated for expression and localization. Together, these two phases will potentially
provide a novel therapeutic strategy for treating metastatic CNS lesions and understanding the
effect of LiFUS on the underlying vascular mechanisms.

## Key facts

- **NIH application ID:** 10474428
- **Project number:** 5F99CA264445-02
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Tasneem Arsiwala
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,243
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474428

## Citation

> US National Institutes of Health, RePORTER application 10474428, Translational use of focused ultrasound to increase blood-tumor barrier permeability as a mechanism to increase drug accumulation into brain metastases of breast cancer (5F99CA264445-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10474428. Licensed CC0.

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