Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines for Quantification of Regional Cardiac Sympathetic Nerve Density With PET
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Composite measure based on radiotracer tissue uptake ratios (heart-to-lung ratio, heart-to-liver ratio, heart-to-blood ratio) and rates of metabolism in plasma (half-time, in minutes) of [18F]4F-MHPG and [18F]3F-PHPG in healthy subjects.
研究概览
简要总结
The purpose of this study is to perform first-in-human PET imaging studies of two new cardiac sympathetic nerve imaging agents, 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and 3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG).
详细描述
In this study, PET imaging studies of two structurally related 18F-hydroxyphenethylguanidines, 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and 3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG) will be performed. All studies will be performed in normal healthy volunteers.
PET stands for Positron Emission Tomography which is a type of imaging that uses a radioactive tracer. This is also called a radiotracer which is a compound linked to a radioactive element. Most compounds are short-lived, meaning that the radioactivity breaks down quickly or is excreted from the body.
In the first stage of the study, dynamic PET imaging for 90 min will be done with [18F]4F-MHPG (n = 4) and [18F]3F-PHPG (n = 4).
Data from these studies will assess each radiotracer's imaging properties, pharmacokinetics and metabolic breakdown in plasma. Application of tracer kinetic analysis methods to the kinetics of each tracer in heart and plasma will be studied to see if these methods can provide accurate measurements of regional nerve sympathetic nerve density in the hearts of human subjects. Results from these initial studies will be used to select the lead compound for further studies in patient populations.
In the second stage of the study, whole-body PET imaging studies (n = 4) with the selected lead radiotracer will be performed to acquire data necessary for generating more accurate human radiation absorbed dose estimates.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Non-obese (BMI < 30)
- •Normal blood pressure
- •Normal blood lipid profile
- •No history of prior cardiovascular disease
- •Not susceptible to claustrophobia
- •Ability to lay flat for 90 min
排除标准
- •Obesity (BMI > 30)
- •Risk factors for heart disease (age > 55y, hypertension, smoking, high blood pressure, high cholesterol levels, diabetes, etc.)
- •History of heart disease (heart attack, atrial fibrillation, ventricular tachycardia, exertional angina)
- •Currently using certain medications that may interact with cardiac nerves (antidepressants, cold medications, nasal decongestants, monoamine oxidase inhibitors, etc.)
- •Claustrophobia
- •Inability to lie flat for 90 min
- •Pregnant or breast feeding
研究组 & 干预措施
Protocol 1: [18F]4F-MHPG
Subjects (n = 4) will be injected one time with 6.5 mCi of 4-[18F]fluoro-meta-hydroxyphenethylguanidine ([18F]4F-MHPG) and receive a 90 minute PET scan.
干预措施: [18F]4F-MHPG (Drug)
Protocol 1: [18F]3F-PHPG
Subjects (n = 4) will be injected one time with 6.5 mCi of 3-[18F]fluoro-para-hydroxyphenethylguanidine ([18F]3F-PHPG) and receive a 90 minute PET scan.
干预措施: [18F]3F-PHPG (Drug)
Protocol 2: Biodistribution Studies
Subjects (n = 4) will be injected one time with 6.5 mCi of either [18F]4F-MHPG or [18F]3F-PHPG (whichever is selected based on Protocol 1 studies) and receive four whole-body PET scans, starting at 5 min, 60 min, 150 min and 360 min after tracer injection.
干预措施: [18F]4F-MHPG (Drug)
Protocol 2: Biodistribution Studies
Subjects (n = 4) will be injected one time with 6.5 mCi of either [18F]4F-MHPG or [18F]3F-PHPG (whichever is selected based on Protocol 1 studies) and receive four whole-body PET scans, starting at 5 min, 60 min, 150 min and 360 min after tracer injection.
干预措施: [18F]3F-PHPG (Drug)
结局指标
主要结局
Composite measure based on radiotracer tissue uptake ratios (heart-to-lung ratio, heart-to-liver ratio, heart-to-blood ratio) and rates of metabolism in plasma (half-time, in minutes) of [18F]4F-MHPG and [18F]3F-PHPG in healthy subjects.
时间窗: 3 months
These data will be used to select the lead radiotracer for further clinical development.
次要结局
- Number of Adverse Events(30 days)
- Radiation Dose(1 year)
研究者
David M. Raffel, Ph.D.
Research Associate Professor
University of Michigan