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

博士项目目标：制造基于无镉结构的新型发光量子点。使F-18与结构表面协调，使它们既具有pet活性又能发光。目的：探讨结构在前列腺癌光学成像和PET成像中的应用。项目描述：前列腺癌（PC）每年影响英国约47700名男性。在英国，前列腺癌是男性最常见的癌症，75岁以上的男性中有35%患有前列腺癌。在主动监测和监视（MRI， PSA和活检）后，目前的主要临床治疗方法之一是手术（机器人辅助根治性前列腺切除术）。然而，由于原发性肿瘤通常难以在前列腺内划定，35%的患者将有阳性肿瘤边缘（即并非所有肿瘤都被切除）。这需要辅助治疗，如放疗，并发症风险较高，治愈机会较低。需要一种新的显像剂，它能与肿瘤特异性结合，准确描绘肿瘤边界，从而为外科医生提供更直接可见的细节，并在机器人前列腺切除术中切除所有癌症，以防止未来复发和进一步的侵入性治疗。具有多模式功能的新型显像剂正在出现，可以对不同尺度长度和不同组织深度的疾病状态进行成像，从而实现更快、更准确的诊断。量子点（QDs）已成为细胞成像的首要纳米材料，具有明亮，稳定和可调谐的发射，与传统的有机染料相比具有许多优点。然而，这些粒子只提供光学发射作为成像能力，这意味着其他强大和互补的技术被忽视了。在本项目中，我们将开发一种基于磷化铟（InP）的无重金属量子点系统，其固有的稳定发射可在可见光谱上调谐。这些颗粒具有被认为是“无重金属”的好处，而传统的含镉材料在常规医院和临床环境中实现量子点应用方面存在主要障碍。目前，基于InP的生物显像剂开始出现在市场上。inp基材料的一个主要优点是与氟的配位，填补了表面缺陷，增强了量子点发射。这种表面刻蚀被认为是改善InP量子点光学性能的关键方法。在这个项目中，我们将使用放射性核素F-18协调到inp基量子点的表面，为我们提供用于成像的发光和PET活性材料。随着F-18衰变为氧，最终材料将是一种具有可控表面氧化层的材料，也被视为稳定发光量子点的关键组成部分。因此，我们不仅拥有一个多模态量子点系统，而且还使用放射性元素作为控制表面工程的方法。我们还将通过将材料与锌合金化并沉积ZnS壳来探索颗粒的结构，以增强发射轮廓，同时保持PET活性。这些颗粒将用于光学显微镜和PET扫描成像各种疾病状态。本项目适合对生物成像感兴趣的合成无机化学家。

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.