18F-PSMA-bioharmonophore conjugates: a smart PET/optical tracer for improved prostate cancer detection and localisation

18F-PSMA-生物配乐团缀合物：用于改进前列腺癌检测和定位的智能 PET/光学示踪剂

• 批准号: 2886605
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2886605
• 关键词: 18F; PSMA; bioharmonophore; conjugates; smart

Aim of the PhD Project:Generate 18F-PSMA-bioharmonophore peptide conjugates as smart imaging agents for prostate diagnosis.Validate the PSMA-PET/nonlinear optics tracer in the detection and localisation of prostate cancer with human tumour tissue.Context of research: Prostate cancer (PCa) is the second most common diagnosed tumour in males worldwide, with over one million new patients diagnosed every year. After PCa diagnosis, the precise determination of the extent of the lesion is a fundamental step for a tailor-made therapy. The earlier the detection and the more precise the diagnosis, the more effective the treatment and the longer the survival. Conventional imaging techniques like CT and MRI face significant limitations, as they cannot detect lesions measuring smaller than a few mm. The most recent nuclear medicine development is the use of prostate specific membrane antigen (PSMA) 18F-PET tracers that are emerging as the most promising tool of medical imaging, gaining ground every day. Yet 18F-PET scans must be interpreted carefully because noncancerous conditions can look like cancer, and some cancers do not appear on PET scans. To increase the predictive value of PET scans, i.e the likelihood that an individual with a positive or negative test result truly has or has not PCa, you will generate a smart diagnostic probe that links PSMA-18F-PET tracers to tripeptides that can self-assemble forming very bright and ultrastable optical imaging probes called bioharmonophores. Successful targeting of such a PET tracer conjugate to PCa cells will lead to their specific accumulation within cells. The proximity of these conjugates in vesicles will facilitate their self-assembly of the bioharmonophore tripeptides generating a high contrast, pH-resistant, non-toxic nonlinear signal with outstanding resolution and predictive value.Potential applications and benefits:The combination of PET imaging and cancer cell-inducible optical imaging of this smart imaging probe will dramatically improve the specificity and the predictive value when compared with conventional PET tracer imaging for (metastatic) prostate cancer. This conjugate will allow for more accurate diagnosis, staging and treatment follow-up in patients with PCa. As 18F-based PET tracers are readily available in most UK trusts, your PSMA-18F-PET tracer conjugate can be easily translated into the clinic.

博士项目的目的：生成18F-PSMA-BIOHARMONOPHORE肽作为前列腺诊断的智能成像剂的结合。对PSMA-PET/非线性光学光学示踪剂在检测和定位前列腺癌与人类肿瘤组织的发现和定位。 PCA诊断后，对病变程度的精确确定是量身定制治疗的基本步骤。检测越早，诊断越精确，治疗越有效，生存时间就越长。常规成像技术（例如CT和MRI）面临着显着的局限性，因为它们无法检测到小于几毫米的病变。最新的核医学发展是使用前列腺特异性膜抗原（PSMA）18F-PET示踪剂，这些示踪剂正在成为最有前途的医学成像工具，每天都在获得地面。然而，必须仔细解释18F-PET扫描，因为非癌状况看起来像癌症，并且有些癌症不会出现在PET扫描中。为了提高PET扫描的预测价值，即具有正面测试结果或阴性测试结果的个体真正具有或没有PCA的可能性，您将生成一个智能诊断探针，将PSMA-18F-PET示踪剂与三肽连接到可以自我组装形成非常明亮和超优化的光学成像探针的三肽。成功靶向这样的宠物示踪剂偶联物将其特异性地积累在细胞中。这些结合物在囊泡中的邻近性将促进它们的自组装，从而产生较高的对比度，耐pH值，无毒的非线性信号，具有出色的分辨率和预测价值。潜在的应用和益处。 （转移性）前列腺癌的宠物示踪剂成像。这种共轭将允许PCA患者进行更准确的诊断，分期和治疗随访。由于大多数英国信托很容易获得18F的宠物示踪剂，因此您的PSMA-18F-PET示踪剂结合物很容易被转化为诊所。