# Optimizing Ultrasound Enhanced Delivery of Therapeutics

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $519,484

## Abstract

Abstract
Pancreatic cancer is the third most common cancer diagnosed in the United States, with more than
43,000 new cases in 2013. It is the fourth leading cause of cancer-related death in both men and women.
Nonetheless, there has been no significant improvement in survival for pancreatic ductal adenocarci-
noma (PDAC) patients over the past 30+ years. For this reason, there is a considerable and urgent
clinical need to develop innovative strategies for effective drug delivery and treatment monitoring, re-
sulting in improved outcomes for patients with PDAC. Our proposal aims at developing contrast-enhanced
ultrasound-mediated image-guided drug delivery (CEUS-IGDD) to be that methodology and to translate it from
the lab to the clinic. The specific tasks are designed to improve the understanding and methodology for control
and monitoring of this IGDD platform, with an initial clinical focus on enhancing the effectiveness of standard
chemotherapeutics for treatment of inoperable PDAC.
 Inherently this project constitutes a multidisciplinary challenge (technological, biological, physical, and
medical), and our strategy to address the critical barriers therefore unites an interdisciplinary team of academic
and industrial investigators from GE Global Research (GE), Haukeland University Hospital and University of
Bergen (together: Bergen), Thomas Jefferson University (TJU), and Rush University Medical Center with
more limited efforts by the Israel Institute of Technology and GlaxoSmithKline (GSK).
 Aim 1 will develop tools and methods to ascertain optimal conditions (acoustic regime, bubble type) for
maximum drug delivery with minimal application of diagnostic-range acoustic energy. Aim 2 utilizes two com-
plementary established pancreatic adenocarcinoma mouse models, using human MIA PaCa-2luc (Bergen) and
PANC-1 (TJU) cell lines. The efficacy of CEUS-IGDD will be evaluated using biodistribution data and quan-
titative imaging methods to monitor treatment response expecting a greater median survival of at least 5
days and a median tumor volume reduction of 50% in the treated group compared to animals receiving
drug alone. The main focus of this proposal is Aim 3, where a three year, multi-center clinical trial en-
rolling one hundred and twenty (120) patients with metastatic or locally advanced and surgically unresectable
PDAC will be conducted at TJU and Bergen. All patients will undergo standard of care chemotherapy, with
one-half receiving adjunctive CEUS-IGDD. Patient outcomes will be compared by quantitative ultrasound as-
sessment, CT imaging including RECIST criteria, ECOG grade, and immunohistochemistry to assess local
progression-free and overall survival with the main endpoint being to increase the number of chemo-
therapy cycles by 75% in the IGDD group relative to controls.

## Key facts

- **NIH application ID:** 9986718
- **Project number:** 5R01CA199646-05
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Flemming Forsberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $519,484
- **Award type:** 5
- **Project period:** 2016-08-25 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986718

## Citation

> US National Institutes of Health, RePORTER application 9986718, Optimizing Ultrasound Enhanced Delivery of Therapeutics (5R01CA199646-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9986718. Licensed CC0.

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