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

博士项目的目的：产生18F-PSMA-bioharmonophore肽缀合物作为智能成像剂用于前列腺诊断。将PSMA-PET/非线性光学示踪剂用于检测和定位人类肿瘤组织中的前列腺癌。研究背景：前列腺癌（PCa）是全球第二大最常见的男性诊断肿瘤，每年有超过100万新患者被诊断。在PCa诊断后，精确确定病变范围是定制治疗的基本步骤。发现得越早，诊断得越准确，治疗就越有效，生存期就越长。传统的成像技术，如CT和MRI面临着重大的局限性，因为它们不能检测测量小于几毫米的病变。最近的核医学发展是使用前列腺特异性膜抗原（PSMA）18F-PET示踪剂，这是新兴的最有前途的医学成像工具，每天都在取得进展。然而，18F-PET扫描必须仔细解释，因为非癌性疾病可能看起来像癌症，而某些癌症不会出现在PET扫描上。为了提高PET扫描的预测价值，即具有阳性或阴性检测结果的个体真正患有或不患有PCa的可能性，您将生成一种智能诊断探针，该探针将PSMA-18F-PET示踪剂与三肽连接，三肽可以自组装形成非常明亮和超稳定的光学成像探针，称为生物谐波载体。将这种PET示踪剂缀合物成功靶向PCa细胞将导致它们在细胞内的特异性积累。这些共轭物在囊泡中的接近将促进它们的bioharmonophore三肽的自组装产生高对比度，耐pH，无毒的非线性信号，具有出色的分辨率和预测value.Potential的应用和好处：PET成像和癌细胞诱导的光学成像的这种智能成像探针的组合将显着提高特异性和预测值相比，与传统的PET示踪剂成像（转移性）前列腺癌。这种结合物将允许对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机构都可以随时获得基于18F的PET示踪剂，因此您的PSMA-18F-PET示踪剂结合物可以轻松地应用于临床。

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.