Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines

Early Phase 1

Completed

Brief Summary: 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).

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Protocol 1: [18F]4F-MHPG	[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.
Protocol 1: [18F]3F-PHPG	[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.
Protocol 2: Biodistribution Studies	[18F]4F-MHPG	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.
Protocol 2: Biodistribution Studies	[18F]3F-PHPG	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.

Primary Outcome Measures

Name	Time	Method
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.	3 months	These data will be used to select the lead radiotracer for further clinical development.

Secondary Outcome Measures

Name	Time	Method
Number of Adverse Events	30 days	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
Radiation Dose	1 year	Human radiation absorbed dose estimates based on the kinetics of the selected lead radiotracer in various organs, as extracted from whole-body PET scans.