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

博士项目目标：生成18f - psma -生物和声团肽偶联物作为前列腺诊断的智能显像剂。验证PSMA-PET/非线性光学示踪剂在人类肿瘤组织中前列腺癌的检测和定位。研究背景：前列腺癌（PCa）是全球男性中第二大最常见的肿瘤，每年有超过100万的新患者被诊断出来。在前列腺癌诊断后，精确确定病变程度是定制治疗的基本步骤。越早发现，诊断越准确，治疗越有效，生存时间越长。传统的成像技术，如CT和MRI，面临着很大的局限性，因为它们不能检测到小于几毫米的病变。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，它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，18F-PET扫描必须仔细解读，因为非癌性疾病可能看起来像癌症，而有些癌症在PET扫描上是看不到的。为了提高PET扫描的预测价值，即具有阳性或阴性测试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，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和超稳定的光学成像探针，称为生物和声团。成功地将这种PET示踪剂偶联物靶向PCa细胞将导致它们在细胞内的特异性积累。这些偶联物在囊泡中的接近性将促进生物和声团三肽的自组装，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。潜在的应用和好处：与传统的PET示踪成像相比，该智能成像探针将PET成像与癌细胞诱导光学成像相结合，将显著提高（转移性）前列腺癌的特异性和预测价值。这种结合将使PCa患者的诊断、分期和治疗随访更加准确。由于基于18f的PET示踪剂在大多数英国信托公司都很容易获得，您的PSMA-18F-PET示踪剂偶联物可以很容易地转化为临床。

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.