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.

博士项目的目标：生成 18F-PSMA-生物和谐肽缀合物作为前列腺诊断的智能成像剂。验证 PSMA-PET/非线性光学示踪剂在人类肿瘤组织中检测和定位前列腺癌的效果。研究背景：前列腺癌 (PCa) 是全球男性中第二常见的诊断肿瘤，每年诊断出的新患者超过一百万。 PCa 诊断后，精确确定病变范围是量身定制治疗的基本步骤。越早发现、诊断越精确，治疗就越有效，生存期也就越长。 CT 和 MRI 等传统成像技术面临很大的局限性，因为它们无法检测小于几毫米的病变。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，该示踪剂正在成为最有前途的医学成像工具，每天都在取得进展。然而，必须仔细解读 18F-PET 扫描，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 扫描中。为了提高 PET 扫描的预测价值，即测试结果呈阳性或阴性的个体确实患有或不患有 PCa 的可能性，您将生成一种智能诊断探针，将 PSMA-18F-PET 示踪剂与三肽连接起来，三肽可以自组装形成非常明亮且超稳定的光学成像探针（称为生物谐波团）。这种 PET 示踪剂缀合物成功靶向 PCa 细胞将导致其在细胞内特异性积累。这些缀合物在囊泡中的接近将促进生物和谐团三肽的自组装，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价值。潜在应用和优势：与传统成像探针相比，这种智能成像探针将PET成像与癌细胞诱导光学成像相结合，将显着提高特异性和预测价值 （转移性）前列腺癌的 PET 示踪成像。这种结合物将有助于对 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使用基于 18F 的 PET 示踪剂，因此您的 PSMA-18F-PET 示踪剂结合物可以轻松应用于临床。