Targeted, radiolabelled near-infrared quantum dots for high sensitivity and resolution, dual modality imaging of human tumours in mice

Aims

The aim of this project is to reduce the number of mice used in preclinical anti-cancer drug development by developing and applying novel near infrared quantum dots (NIR-QDs) to improve the sensitivity and resolution of preclinical imaging. This will increase the amount of information generated in each animal, reducing the overall number of animals required per study.

Background

Current models used for testing anti-cancer drugs are often not very representative of real patient tumours and so may not correctly identify drugs likely to work well in the clinic. Imaging the growth of cancer cells in animal models, and monitoring the way that the different cells within the tumours behave and interact with each other, which are important in determining drug response, is difficult with current methods. This project will develop novel NIR-QDs which fluoresce at a higher wavelength than currently available standard fluorescent probes. This will provide a more sensitive imaging approach, allowing signals to be detected at deeper sites within the body and improving the quality of the images obtained.

The application of these new probes will allow (i) more detailed information to be gained from each animal used, (ii) repeat imaging of the same animal over time, and (ii) the use of advanced models which provide more relevant information about how useful a drug is likely to be in the clinic.

Research details and methods

The NIR-QDs developed during the course of this project will be designed so that they do not photo-bleach, will be water-soluble, and optically active in the NIR wavelength, providing improved tissue penetration and sensitivity. They will incorporate targeting ligands for uptake by specific populations of cells within the tumour which will allow the growth and drug response of cancer cells or supporting cells within the tumours to be followed. They will also include a positron-emitting radionuclide label which will allow them to be used for positron emission tomography (PET) imaging as well as fluorescence imaging, which will provide a further improvement in the resolution of the images that can be obtained, and will facilitate dual imaging in the same animal.

• Further Funding: NC3Rs PhD Studentship, Application of a 3D hydrogel-based model to replace use of animals for passaging patient-derived xenografts, April 2017, £90,000
• Further Funding: NC3Rs Project Grant, The human tumour micro-environment modelled in in vitro biomatrices and applied to cancer drug discovery, October 2009, £407,235