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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Protocol 1: [18F]4F-MHPG | Experimental | 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. |
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| Protocol 1: [18F]3F-PHPG | Experimental | 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. |
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| Protocol 2: Biodistribution Studies | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [18F]4F-MHPG | Drug | IV injection of [18F]4F-MHPG |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | These data will be used to select the lead radiotracer for further clinical development. | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Radiation Dose | Human radiation absorbed dose estimates based on the kinetics of the selected lead radiotracer in various organs, as extracted from whole-body PET scans. | 1 year |
| Number of Adverse Events |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David M Raffel, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30558502 | Derived | Raffel DM, Jung YW, Koeppe RA, Jang KS, Gu G, Scott PJH, Murthy VL, Rothley J, Frey KA. First-in-Human Studies of [18F] Fluorohydroxyphenethylguanidines. Circ Cardiovasc Imaging. 2018 Dec;11(12):e007965. doi: 10.1161/CIRCIMAGING.118.007965. |
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| ID | Term |
|---|---|
| D001342 | Autonomic Nervous System Diseases |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C583191 | 4-fluoro-3-hydroxyphenethylguanidine |
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| [18F]3F-PHPG | Drug | IV injection of [18F]3F-PHPG |
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Number of study participants with adverse events as a measure of safety and tolerability following intravenous administration of [18F]4F-MHPG or [18F]3F-PHPG
| 30 days |