MICA: DCS - Evaluation of [18F]fluoroethyl triazole labelled [Tyr3]Octreotate analogues for the imaging of neuroendocrine tumours

MICA：DCS - [18F]氟乙基三唑标记的[Tyr3]奥曲酸类似物用于神经内分泌肿瘤成像的评估

• 批准号: MR/J007986/1
• 负责人: Eric Aboagye
• 金额: $ 99.56万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ007986%2F1
• 关键词: MICA; DCS; Evaluation; 18F; fluoroethyl

The incidence and prevalence of gastroenteropancreatic neuroendocrine tumours (NETs) has been increasing over the past three decades. Due to the high density of somatostatin receptors (SSTR), mainly SSTR2, on the cell surface of these tumours, imaging of tumours is possible. Existing technologies have poor sensitivity and so new methods are being explored. One potential area is the use of 18F-labelled tracers for Positron Emission Tomography (PET) scanning which are much more sensitive and specific to the tumours of interest than exisiting tracers and also have a reduced scanning time. Previous work by this group, under a Developmental Pathway Funding Scheme (DPFS) award, designed five structurally-related [18F]-fluoroethyltriazole-[Tyr3]octreotate analogues. Based on the findings of this work, one candidate compound ( [18F]-FET-betaAG-TOCA) was chosen as the lead compound to take forward into clinical development. We propose to develop [18F]-FET-betaAG-TOCA clinically via a 2 stage trial design. The initial study will assess the pharmacokinetics (PK), biodistribution and safety of the novel tracer employing 'whole body dynamic PET scanning'; of particular interest will be the optimal time for imaging. Using this information we will construct an appropriate protocol for 'whole body static PET scanning' in the subsequent study. We will then compare the diagnostic efficacy of [18F]-FET-betaAG-TOCA PET/CT to [68Ga]-DOTATATE PET/CT (a method currently used for NETs) in patients with a histological diagnosis of NET. These clinical studies will be used as the basis for future larger clinical trials and a Department of Health application to establish this tracer as the new clinical standard based on equivalent sensitivity and specificity but improved kinetics and handling, as well as ease of GMP manufacturing than the existing [68Ga]-DOTATATE PET/CT.

胃肠胰腺神经内分泌肿瘤（NETs）的发病率和患病率在过去三十年中一直在增加。由于生长抑素受体（SSTR），主要是SSTR 2，在这些肿瘤的细胞表面的高密度，肿瘤的成像是可能的。现有技术的灵敏度很差，因此正在探索新的方法。一个潜在的领域是使用18F标记的示踪剂进行正电子发射断层扫描（PET），其对感兴趣的肿瘤比示踪剂更敏感和特异，并且还具有减少的扫描时间。该小组先前的工作，在发展途径资助计划（DPFS）奖下，设计了五种结构相关的[18F]-氟乙基三唑-[Tyr 3]奥曲酸类似物。根据这项工作的结果，选择一种候选化合物（[18 F]-FET-betaAG-TOCA）作为先导化合物，以推进临床开发。我们建议通过2阶段试验设计在临床上开发[18 F]-FET-betaAG-TOCA。最初的研究将采用“全身动态PET扫描”评估新型示踪剂的药代动力学（PK）、生物分布和安全性;特别感兴趣的是成像的最佳时间。利用这些信息，我们将在随后的研究中构建一个合适的“全身静态PET扫描”协议。然后，我们将在组织学诊断为NET的患者中比较[18 F]-FET-betaAG-TOCA PET/CT与[68 Ga]-DOTATATE PET/CT（目前用于NET的方法）的诊断有效性。这些临床研究将用作未来更大规模临床试验和卫生部申请的基础，以建立这种示踪剂作为新的临床标准，其基于等效的灵敏度和特异性，但改进的动力学和处理，以及比现有的[68 Ga]-DOTATATE PET/CT更易于GMP制造。

项目成果

Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia.

• DOI: 10.1039/c5dt02537k
• 发表时间: 2016-01-07
• 期刊: Dalton transactions (Cambridge, England : 2003)
• 作者: Alam IS;Arrowsmith RL;Cortezon-Tamarit F;Twyman F;Kociok-Köhn G;Botchway SW;Dilworth JR;Carroll L;Aboagye EO;Pascu SI
• 通讯作者: Pascu SI

Optimal method for metabolic tumour volume assessment of cervical cancers with inter-observer agreement on [18F]-fluoro-deoxy-glucose positron emission tomography with computed tomography.

• DOI: 10.1007/s00259-020-05136-8
• 发表时间: 2021-06
• 期刊: European journal of nuclear medicine and molecular imaging
• 影响因子: 9.1
• 作者: Arshad MA;Gitau S;Tam H;Park WE;Patel NH;Rockall A;Aboagye EO;Bharwani N;Barwick TD
• 通讯作者: Barwick TD

The anticancer gene ORCTL3 targets stearoyl-CoA desaturase-1 for tumour-specific apoptosis.

• DOI: 10.1038/onc.2014.93
• 发表时间: 2015-03-26
• 期刊: Oncogene
• 影响因子: 8