Luminescent/PET-active quantum dots for multimodal imaging of prostate cancer

Aim of the PhD Project:

To manufacture new luminescent quantum dots based on cadmium-free structures.
To coordinate F-18 to the surface of the structures, making them both PET-active and luminescent.
To use structures in optical imaging and PET imaging of prostrate cancer.

Project Description:

Prostate cancer (PC) affects around 47,700 men in the UK each year. In men, it is the most common cancer in the UK with 35% of over 75's having PC. After active monitoring and surveillance (MRI, PSA and biopsies), one of the current primary clinical treatments is surgery (robot-assisted radical prostatectomy) However, as the primary tumour is often difficult to delineate within the prostate gland, 35% of patients will have a positive tumour margin (i.e. not all of the tumour is resected). This requires adjuvant treatment, e.g. radiotherapy with higher risks of complications and lower chance of cure. A new imaging agent is needed that binds specifically to the tumour, to give accurate delineation of the tumour boundaries, therefore providing the surgeon with more direct visible detail and the ability to remove all of the cancer during robotic prostatectomy, to prevent future reoccurrence and further invasive therapy.

New imaging agents are emerging with multimodal capabilities, allowing imaging of disease states at different scale lengths and different tissue depths, resulting in quicker and more accurate diagnoses. Quantum dots (QDs) have emerged as the premier nanomaterial for cellular imaging, having bright, stable and tuneable emission, offering numerous benefits over traditional organic dyes. The particles, however, only offer optical emission as an imaging capability which means other, powerful and complimentary techniques are over-looked.

In this project, we will develop a heavy metal-free quantum dot system based on indium phosphide (InP), with inherent stable emission tuneable over the visible spectrum. These particles have the benefit of being considered 'heavy metal-free', with classical cadmium containing materials presenting a major hindrance in realising QD applications in routine hospital and clinical settings. Currently, InP based biological imaging agents are beginning to emerge on the market.

A major advantage of InP-based materials is their coordination with fluorine, which fills surface defects and enhances QD emission. This surface etching is considered a key method for improving the optical properties of InP QDs. In this project, we will use the radionuclide F-18 to coordinate to the surface of InP-based QDs providing us with luminescent and PET active materials to be used in imaging. As F-18 decays to oxygen, the final material will be a material with a controlled surface oxide layer, also seen as key component to stable luminescent quantum dots. We therefore not only have a multimodal QD system, but also use the radioactive element as a method for controllably engineering the surface.

We will also explore the structure of the particle by alloying the material with zinc and depositing a ZnS shell with a view to enhancing the emissive profiles, whilst maintaining PET activity. These particles will be used in imaging various disease states with both optical microscopy and PET scans. This project would suit a synthetic inorganic chemist with an interest in biological imaging.

Strains on the healthcare system in the UK create an acute need for finding more effective, efficient, safe, and accurate non-invasive imaging solutions for clinical decision-making, both in terms of diagnosis and prognosis, and to reduce unnecessary treatment procedures and associated costs. Medical imaging is currently undergoing a step-change facilitated through the advent of artificial intelligence (AI) techniques, in particular deep learning and statistical machine learning, the development of targeted molecular imaging probes and novel "push-button" imaging techniques. There is also the availability of low-cost imaging solutions, creating unique opportunities to improve sensitivity and specificity of treatment options leading to better patient outcome, improved clinical workflow and healthcare economics. However, a skills gap exists between these disciplines which this CDT is aiming to fill.

Consistent with our vision for the CDT in Smart Medical Imaging to train the next generation of medical imaging scientists, we will engage with the key beneficiaries of the CDT: (1) PhD students & their supervisors; (2) patient groups & their carers; (3) clinicians & healthcare providers; (4) healthcare industries; and (5) the general public. We have identified the following areas of impact resulting from the operation of the CDT.

- Academic Impact: The proposed multidisciplinary training and skills development are designed to lead to an appreciation of clinical translation of technology and generating pathways to impact in the healthcare system. Impact will be measured in terms of our students' generation of knowledge, such as their research outputs, conference presentations, awards, software, patents, as well as successful career destinations to a wide range of sectors; as well as newly stimulated academic collaborations, and the positive effect these will have on their supervisors, their career progression and added value to their research group, and the universities as a whole in attracting new academic talent at all career levels.

- Economic Impact: Our students will have high employability in a wide range of sectors thanks to their broad interdisciplinary training, transferable skills sets and exposure to industry, international labs, and the hospital environment. Healthcare providers (e.g. the NHS) will gain access to new technologies that are more precise and cost-efficient, reducing patient treatment and monitoring costs. Relevant healthcare industries (from major companies to SMEs) will benefit and ultimately profit from collaborative research with high emphasis on clinical translation and validation, and from a unique cohort of newly skilled and multidisciplinary researchers who value and understand the role of industry in developing and applying novel imaging technologies to the entire patient pathway.

- Societal Impact: Patients and their professional carers will be the ultimate beneficiaries of the new imaging technologies created by our students, and by the emerging cohort of graduated medical imaging scientists and engineers who will have a strong emphasis on patient healthcare. This will have significant societal impact in terms of health and quality of life. Clinicians will benefit from new technologies aimed at enabling more robust, accurate, and precise diagnoses, treatment and follow-up monitoring. The general public will benefit from learning about new, cutting-edge medical imaging technology, and new talent will be drawn into STEM(M) professions as a consequence, further filling the current skills gap between healthcare provision and engineering.

We have developed detailed pathways to impact activities, coordinated by a dedicated Impact & Engagement Manager, that include impact training provision, translational activities with clinicians and patient groups, industry cooperation and entrepreneurship training, international collaboration and networks, and engagement with the General Public.