Application of Clinical Biomarkers for the Development of Multimodal Imaging Agents

“晚期癌症患者的癌症分期不正确是导致一线癌症治疗选择不正确的原因，导致死亡率增加（1.5- 2倍）和生存率降低（少于12个月），在英国多达25%的癌症诊断患者中。对比增强MR和CT成像是所有治疗方案中最常见的癌症成像和分期成像方式。目前的MR/CT成像对比成像剂不具备所需的特异性和灵敏度，因此无法区分癌症亚阶段，导致癌症分期的估计不准确和不精确。该项目开发“新型”，即患者特异性、MR/CT成像敏感且无副作用的成像剂。成像剂由多功能纳米颗粒和癌症生物标志物靶向配体组成。纳米颗粒具有生物相容性，能够优化MR和CT成像中的对比度。最重要的是，纳米颗粒剂特异性结合癌细胞，因此，相对于现有的MR/CT成像造影剂，需要低4- 10倍的剂量来优化肿瘤对比度，因此对患者造成的不便和副作用最小。显像剂不仅可以减少患者临床就诊的时间和频率，而且还可以通过增加癌症的总体治疗费用来降低癌症治疗的总体费用。通过最大限度地减少翻修手术、影像学检查和相关的低效率来提高治疗效果。因此，个性化的成像剂将通过使癌症患者能够获得充分和具有成本效益的医疗保健来促进可持续的医疗保健。"

"Incorrect assignment of cancer stage in advanced-cancer-patients is responsible for the incorrect choice of first-line cancer therapy leading to increased-mortality(1.5-2x) and lowered-survival (less than 12 months) in as-many-as 25% of all patients diagnosed with cancer in the UK.Contrast-enhanced MR and CT imaging are the most common imaging modalities for cancer imaging and staging across all treatment regimes. Current MR/CT imaging contrast imaging agents do not possess required specificity and sensitivity and therefore cannot distinguish between cancer sub-stages, resulting in an inaccurate and imprecise estimation of cancer stage.The project develops ""novel"" i.e. patient-specific, MR/CT imaging-sensitive and side-effects-free imaging agents. The imaging agents are composed of multifunctional nanoparticles and cancer biomarker targeting ligands. The nanoparticles are biologically compatible and capable of optimizing contrast in MR and CT imaging. Most importantly, the nanoparticle agents specifically bind to cancer cells, therefore, are required in 4-10x lower dosage relative to existing MR/CT imaging contrast agents to optimize tumour contrast, thus causing minimum inconvenience and adverse effects in patients.The imaging agents will not only reduce the time and frequency of patient's clinical visits but also reduce the overall cost of cancer treatment by increasing overall cancer treatment efficacy by minimizing revision surgeries, imaging sessions and related-inefficiencies. Therefore the personalized imaging agents will promote sustainable healthcare by enabling cancer patient's access to adequate and cost-effective healthcare."