Theme leader: Professor Andrew Whittaker, University of Queensland
Image: Proposed design for a stimuli-responsive theranostic nanoparticle in which both MRI and PET imaging moieties are combined. Upon decreasing pH, which is common for the tumour microenvironment, the biochemical properties of the nanoparticle are changed. As a result, the nanoparticle becomes more accessible to water molecules, thereby increasing MR contrast.
Fluorescence, magnetic resonance imaging, X-ray computed tomography and positron emission tomography agents have led to major advances in our understanding of diseased tissue. Often these are blood flow agents that accumulate in the tissue of origin due to changes in the local blood flow. For example the “leaky vasculature” within cancerous tissue can be taken advantage of to allow permeation and retention of imaging agents in tumours. Such simple agents however, cannot be targeted to specific diseases (or even specific tumours), and are poor at detecting the early stages of disease and/or small tissue volumes.
The programs within the Imaging Technologies theme of the CBNS focus on these challenges, aiming to identify novel, safe and more effective imaging agents. The issues of selectivity, specificity, responsiveness and lifetime are tackled using polymer-based imaging agents. Using a macromolecular strategy allows, for example, superior relaxivity for paramagnetic MRI contrast agents (thereby addressing sensitivity issues) and also provides control over nanostructure and therefore in vivo lifetimes and clearance. Specificity can be achieved by modifying polymeric imaging agents with bio-recognition molecules such as antibodies in conjunction with other programs within the CBNS.
In collaboration with the Delivery Systems theme, imaging particles are made responsive using molecular beacons which can be interrogated to provide information on cell function or local metabolic processes. Simple examples of this are agents that can be designed to respond to changes in temperature, pH, redox potential, hypoxia, etc. Imaging agents responsive to oxygen tension, or specific ions can be envisaged and polymeric architecture provides very distinct advantages in the design of these molecules.
The key scientific goals of the Imaging Technologies theme are:
- to develop imaging agents with high specificity for particular tissue types and diseases, specifically determining the most effective targeting strategies;
- to design imaging agents that are responsive to biological triggers, so that certain pathologies, for example hypoxia, inflammation and cancerous tissue can be identified;
- to investigate how the structure of imaging agents influences the lifetime in vivo, so that clearance of the imaging agent can be controlled to ensure appropriate cellular uptake and removal of the agent from the body; and
- to investigate the design requirements to optimise sensitivity of imaging agents, to allow early detection of disease and to identify the margins of diseased tissue.
CBNS Annual Reports provide details of the various activities within the Imaging Technologies theme.