Evaluation of [18F]Fluoroethyl Triazole Labelled [Tyr3]-Octreotate Analogues for the Imaging of Neuroendocrine Tumours.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 主要终点
- To Determine the Biodistribution of [18F] Following Single I.V Administration of [18F]-FET-βAG-TOCA Injection in Patients With a Histological Diagnosis of NET.
研究概览
简要总结
Radiolabelled somatostatin analogs are invaluable in the diagnosis and treatment of neuroendocrine tumours (NET). The most common positron emission tomography (PET) radiotracers used for the visualisation of NET are radiolabelled somatostatin analogs (SSAs) labelled with [68Ga]Ga-DOTA-peptides. However, [68Ga]Ga-DOTA-peptide radiolabelled SSAs have significant limitations in terms of accessibility and low throughput. The team at Imperial College London developed a novel radiotracer, [18F]fluoroethyl triazole labelled [Tyr3]-Octreotate analogue ([18F]-FET-βAG-TOCA), in an attempt to overcome these limitations. The FETONET study was designed to have 3 parts. The FETONET study was designed to have 3 parts. Part A evaluated the biodistribution, dosimetry and safety of [18F]FET-βAG-TOCA. Uptake was assessed at multiple time points over a 4 hour period. The data was analysed and an optimal imaging time point determined. Part B of the FETONET study involved the performance of whole body static [18F]FET-βAG-TOCA PET-CT imaging, at the optimal time point previously established, within a larger cohort of patients. Part C comprised a prospective non-inferiority study that analysed the [18F]FET-βAG-TOCA PET/CT data collected within Part A & Part B and compared this to standard of care [Ga68]Ga-DOTA-peptide PET-CT imaging.
详细描述
Neuroendocrine tumours (NET) are tumours derived from enterochromaffin cells, which are characterised by the expression of somatostatin receptors (SSTRs) on their surface. These tumours release substances into systemic circulation, resulting in episodic flushing, wheezing, diarrhoea, and eventual right-sided valvular heart disease. All of these symptoms negatively impact on patients' quality of life. The management of NET is primarily determined by the stage of disease. For patients with localised or limited disease the primary modality of therapy is surgery. Whilst patients with metastatic disease, undergo systemic therapy with palliative intent. Accurate imaging is therefore central to the management of this disease. Whilst computed tomography (CT) is useful in the localisation of NET, nuclear imaging using tumour-specific radiolabelled receptors are considerably more sensitive and specific methods for detecting NET and their metastases. The most commonly used positron emission tomography (PET) radiotracers used for the visualisation of NET are radiolabelled somatostatin analogs (SSAs) labelled with [68Ga]Ga-DOTA-peptides. The [68Ga]Ga-DOTA-peptide radiolabelled SSAs have significant limitations in terms of accessibility and low throughput. The team at Imperial College London developed a novel radiotracer, [18F]fluoroethyl triazole labelled [Tyr3]-Octreotate analogue ([18F]-FET-βAG-TOCA), in an attempt to overcome these limitations. The FETONET study was designed to have 3 parts. The FETONET study was designed to have 3 parts. Part A evaluated the biodistribution, dosimetry and safety of [18F]FET-βAG-TOCA. Uptake was assessed at multiple time points over a 4 hour period. The data was analysed and an optimal imaging time point determined. Part B of the FETONET study involved the performance of whole body static [18F]FET-βAG-TOCA PET-CT imaging, at the optimal time point previously established, within a larger cohort of patients. Part C comprised a prospective non-inferiority study that analysed the [18F]FET-βAG-TOCA PET/CT data collected within Part A & Part B and compared this to standard of care [Ga68]Ga-DOTA-peptide PET-CT imaging.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Age ≥ 18 years
- •Histological diagnosis of NET of any site, except where ENETS criteria does not mandate histology for confirmation of diagnosis or patients who have a positive 68Gallium-peptide scan in whom NET diagnosis is pre-operatively definitive.
- •Locally advanced or metastatic disease.
- •Eastern Cooperative Oncology Group (ECOG) performance status of <2 (appendix A).
- •Life expectancy > 3 months.
- •Measurable disease defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥10mm using conventional techniques.
- •Somatostatin receptor imaging within 6 months. (if patient does not have somatostatin receptor imaging they may also be included provided they have measurable disease (≥10mm) on conventional imaging.
- •Adequate organ system function as defined within Table 1.
排除标准
- •Patients received chemotherapy within 3 weeks of study.
- •Patients received radiotherapy within 4 weeks of study.
- •Active uncontrolled infections, gastrointestinal disease, haemolysis or any serious co-existing medical illness.
- •Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- •Pregnant or lactating women.
- •Females of childbearing potential who are unwilling to avoid pregnancy, for the duration of the study.
- •Presence of any underlying medical conditions which in the investigators opinion would make the patients unsuitable for treatment.
- •Patient not expected to be able to tolerate the scanning sessions.
研究组 & 干预措施
Part A: [18F]-FET-βAG-TOCA-PET/CT performed in patients with histologically-confirmed NET.
Patients with histologically-confirmed neuroendocrine tumours (NET) enrolled into Part A of the FETONET study underwent whole-body dynamic [18F]FET-βAG-TOCA imaging at multiple time points over a 4 hour period, with sampling of venous bloods for radioactivity and radioactive metabolite quantification.
干预措施: [18F]-FET-βAG-TOCA (Drug)
Part B: [18F]FET-βAG-TOCA PET/CT compared with [68Ga]Ga-DOTA-peptide PET/CT in patients with NET.
Patients with histologically confirmed neuroendocrine tumours (NET) underwent PET/CT imaging with both [18F]FET-βAG-TOCA and [68Ga]Ga-DOTA-peptide. The two PET/CT scans were performed within a 6-month time period. Whole-body static [18F]FET-βAG-TOCA PET/CT scan performed at 50 minutes post radiotracer injection.
干预措施: [18F]-FET-βAG-TOCA (Drug)
结局指标
主要结局
To Determine the Biodistribution of [18F] Following Single I.V Administration of [18F]-FET-βAG-TOCA Injection in Patients With a Histological Diagnosis of NET.
时间窗: Baseline (on day of scan over 4 hours)
Mean residence time (MRT) was used to characterise the biodistribution of \[18F\]-FET-βAG-TOCA throughout the body. Mean residence time is a pharmacokinetic/uptake parameter that describes the average length of time a radiotracer resides within the body, or a particular organ, before being eliminated. Understanding MRT helps researchers to determine how long a radiotracer remains in the system, which is crucial for drug dosing, therapeutic efficacy, and potential toxicity assessment.
To Calculate the Effective Dose (ED) of [18F]-FET-βAG-TOCA
时间窗: Baseline (on the day of the scan over 4 hours)
Effective dose is an estimate of the overall risk of potential harm from exposure to ionising radiation. ED takes into account, the absorbed dose to all organs of the body, the relative harm level of the radiation and the sensitivities of each organ to radiation. ED may help in understanding the risk of potential long-term health effects from radiation exposure, such as the risk of developing cancer later in life. The unit of measure for ED is millisievert per megabecquerel (mSv/MBq), which refers to the effective dose (amount of radiation absorbed by the body) per unit of activity administered.
To Assess Tumoural Uptake of [18F]-FET-βAG-TOCA
时间窗: Baseline (on the scan day over 4 hours)
Standardised uptake value (SUV) is a semiquantitative measurement of radiotracer uptake in tissue. It is a ratio that compares the activity concentration in a specific region of interest to the activity concentration in the whole body. SUVmax is the highest value of the SUV measured within a region of interest.
次要结局
- To Compare the Diagnostic Efficacy of [18F]-FET-βAG-TOCA PET/CT With Standard of Care Somatostatin Receptor Imaging in Patients With a Histological Diagnosis of NET.([68Ga]Ga-DOTA-peptide PET/CT imaging performed within 6 months of the [18F]-FET-βAG-TOCA PET/CT scan.)
- Comparison of [18F]-FET-βAG-TOCA PET/CT Scan and Central Review (Nuclear Medicine and Radiology Physician Experts) of All Imaging Received.([68Ga]Ga-DOTA-peptide PET/CT imaging assessed within 6 months of the [18F]-FET-βAG-TOCA PET/CT scan.)