Contrast Enhanced Ultrasound with Therapeutic Modality
Principal Investigator: Margaret Wheatley
Abstract: Recent advances in contrast agent (CA) development have expanded the range of diagnostic ultrasound (US), an imaging modality that has the advantage of being safe, real-time, inexpensive and portable. The challenge now becomes the differentiation of soft tissue metastases in organs such as the liver and breast, imaging of actual and potential disease states such as atherosclerotic plaque or regions of ischemia, and discrimination between malignant and benign. Moreover the potential of a therapeutic role for US, using imaging to guide and trigger drug delivery presents exciting new areas of research. The long-term objective is to develop a polymer-based US contrast agent with therapeutic capabilities. The goal is to both image and target release of a drug from the CA using the same US energy. The polymer CA should enhance the diagnostic image and aid the physician in locating diseased tissue. The agent must be non toxic, biocompatible, biodegradable and stable after injection for the duration of imaging. It must pass unimpeded through the capillary bed, (be less than -6 pm in diameter). The first aim is to develop a CA that is echogenic in the medical imaging range, (1-10 MHz) and stable in vivo giving a clear diagnostic image and have the potential to deliver a drug. The second is to attach a drug onto the surface of the CA and to use focused US to visualize and release the exact dose of drug at the time and location required. Specific Aim 1: To develop, optimize and characterize a biodegradable polymer CA with characteristics that enable it to function as a drug carrier and delivery system. Specific Aim 2: To characterize the degradation pattern of the hollow polymer microcapsules, with and without US of different frequencies. Specific Aim 3: To investigate incorporation of bioactive compounds into the polymer capsule shell. Determination will be made of the method which yields the greatest payload of the bioactive compound and which reduces any initial burst effect. Specific Aim 4: To determine the effects of ultrasound energy on the bioactive compound release rate and pattern from the contrast agent, the effect of ultrasound on the compound activity and the effect of payload on acoustic properties. To understand the effects of the ultrasound parameters, frequency, pressure and energy on the drug release profile, and investigate the mechanism of drug release, in order to better control the release profile. Specific Aim 5: Investigate acoustically-triggered drug delivery in vitro using tissue cultured breast cancer cell lines. Optimized drug-loaded capsules will be tested for efficacy of bioactive compound release by assessing cell damage in tissue cultures, compared with blank capsules and with US alone. These studies are a prelude to show feasibility prior to in vivo studies.
Funding Period: 2003-09-01 - 2007-02-28
more information: NIH RePORT