Phase IIa Clinical Trial: Feasibility Study on Non-Invasive Simultaneous Hyperpolarized [1-13C]Pyruvate Magnetic Resonance Spectroscopy and 18F-FDG PET (hyperPET) for Metabolic Imaging in Patients With Cancer
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Whole-tumor lactate/pyruvate ratio measured with MRS
研究概览
简要总结
Prospective phase 2a clinical trial to demonstrate proof-of-concept for simultaneous hyperpolarized [1-13C]pyruvate and 18F-FDG for positron emission tomography (PET) and MRS (magnetic resonance spectroscopy) in a PET/MR scanner in patients with cancer.
详细描述
PET imaging with 18F-FDG is a well established method for non invasively assessing the intracellular glucose accumulation. 18F-FDG PET is used in many applications with diagnosing and staging of patients with cancer being one of the primary indications. Once internalized into the cell, 18F-FDG is phosphorylated to the metabolically inactive 18F-FDG-6-phosphate. Therefore it is not possible to determine what happens to the downstream glucose metabolites. In particular, it is not possible to determine the conversion into lactate, which is upregulated in many cancers. The upregulation of lactate conversion in cancers, even in presence of oxygen, is known as the Warburg effect.
Hyperpolarized [1-13C]pyruvate MRS makes is possible to circumvent this limitation. The technique makes is it possible to follow the downstream fate of the glycolysis intermediate, pyruvate, and in particular makes is is possible to non-invasively and in in real time measure the glycolytic conversion of pyruvate into lactate as a direct measure of the Warburg effect.
When using a PET/MR scanner, it is possible to simultaneous measure the glucose influx with 18F-FDG and the conversion of pyruvate into lactate with hyperpolarized [1-13C]pyruvate. In this way, the two modalities provide complementary information on the in vivo glycose metabolism.
The prospective phase 2a project will include up to 15 patients diagnosed with breast cancer, gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) of all grades (G1, G2, G3)., lymphomas or sarcomas The aim is to demonstrate proof-of-concept for the feasibility of simultaneous acquisition of hyperpolarized [1-13C]pyruvate MRS and 18F-FDG PET imaging in a PET/MR scanner in cancer patients to allow for simultaneous measurements of overall tumor pyruvate-to-lactate conversion parameters on MRS and glucose influx with 18F-FDG on PET.
Included patients are injected with a standard dose of radioactive 18F-FDG. Subsequent dynamic PET acquisition is performed for up to 90 minutes after injection on an area-of-interest covering pre-specified tumor lesion(s). Regional anatomical magnetic resonance imaging (MRI) is performed, including diffusion weighted imaging (DWI) and contrast enhanced imaging (DCE). MRS/MRSI is performed following the injection(s) of hyperpolarized [1-13C]Pyruvate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Diagnosed with breast cancer, gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) grades G1, G2 or G3, lymphoma or sarcoma
- •Measurable solid tumor of at least 1.5 cm
- •Capable of understanding the patient information in Danish and giving full informed consent
排除标准
- •Pregnancy
- •Breast-feeding
- •Weighs above 140 kg and/or with abdominal circumference exceeding the gantry of the PET/MR coil (120 cm)
- •History of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FDG or pyruvate
- •Patients who are unable to lie in the MR scanner for up to 90 minutes
- •Pace-maker
- •Metallic implantations within the past 6 weeks
- •Non-MR compatible implants
- •Claustrophobia
- •Participants who have not fasted for a minimum of 4 hours prior to the planned scan time
研究组 & 干预措施
Experimental
Injection of 18F-FDG and injections of hyperpolarized [1-13C]Pyruvate and subsequent PET/MRI/MRS scan
干预措施: 18F-FDG (Drug)
Experimental
Injection of 18F-FDG and injections of hyperpolarized [1-13C]Pyruvate and subsequent PET/MRI/MRS scan
干预措施: Injection of hyperpolarized [1-13C]Pyruvate (Drug)
Experimental
Injection of 18F-FDG and injections of hyperpolarized [1-13C]Pyruvate and subsequent PET/MRI/MRS scan
干预措施: PET/MR/MRS/MRSI scanning (Procedure)
结局指标
主要结局
Whole-tumor lactate/pyruvate ratio measured with MRS
时间窗: Up to 10 minutes after injection of hyperpolarized [1-13C]Pyruvate
Whole-tumor lactate/pyruvate ratio measured with MRS in regions-of-interest covering the tumor lesion(s) following injection of hyperpolarized \[1-13C\]Pyruvate
Whole-tumor glucose uptake measured with PET (static)
时间窗: Approximately 60 minutes after injection of 18F-FDG
Whole-tumor standardized uptake values (SUV): SUVmean and SUVmax measured with PET in regions-of-interest covering the tumor lesion(s) approximately 60 minutes after injection of 18F-FDG
Correlation between whole-tumor lactate/pyruvate ratio measured with MRS and tumor glucose uptake measured with PET (static)
时间窗: Approximately 60 minutes after injection of 18F-FDG
Correlation between whole-tumor lactate/pyruvate ratio measured with MRS and whole-tumor SUVmean and SUVmax measured with PET in regions-of-interest covering the tumor lesion(s)
Correlation between whole-tumor lactate/pyruvate ratio measured with MRS and tumor glucose uptake measured with PET (dynamic)
时间窗: Up to 90 minutes after injection of 18F-FDG
Correlation between whole-tumor lactate/pyruvate ratio measured with MRS and whole-tumor Ki measured with PET in regions-of-interest covering the tumor lesion(s)
Whole-tumor glucose uptake measured with PET (dynamic)
时间窗: Up to 90 minutes after injection of 18F-FDG
Whole-tumor glucose influx rate constant (Ki) derived from dynamic PET in regions-of-interest covering the tumor lesion(s) following injection of 18F-FDG
次要结局
- Correlation between measurements of in vivo glycolytic markers based on PET/MRS and enzymes involved in glycolytic metabolism based on ex vivo analyses(Up to 90 minutes after injection of 18F-FDG)
研究者
Mathias Loft
Principal Investigator
Rigshospitalet, Denmark