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Smart Imaging Probes, Emerging Imaging

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

Project ID: 2021_019

Student: Jack Oldroyd

1st Supervisor: Mark Green, King’s College London
2nd Supervisor: Graeme Stasiuk, King’s College London
Clinical Champion: Prokar Dasgupta, King’s College London

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 / Background:

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.

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