Clinical Translation of 18F-Labeled Hydroxyphenethylguanidines

NCT ID: NCT02385877

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-08-31

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.

Conditions

Autonomic Peripheral Nervous System Diseases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

[18F]4F-MHPG

Intervention Type: DRUG

IV injection of \[18F\]4F-MHPG

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.

Group Type: EXPERIMENTAL

[18F]3F-PHPG

Intervention Type: DRUG

IV injection of \[18F\]3F-PHPG

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.

Group Type: EXPERIMENTAL

[18F]4F-MHPG

Intervention Type: DRUG

IV injection of \[18F\]4F-MHPG

[18F]3F-PHPG

Intervention Type: DRUG

IV injection of \[18F\]3F-PHPG

Interventions

[18F]4F-MHPG

IV injection of \[18F\]4F-MHPG

Intervention Type: DRUG

[18F]3F-PHPG

IV injection of \[18F\]3F-PHPG

Intervention Type: DRUG

Other Intervention Names

4-[18F]fluoro-meta-hydroxyphenethylguanidine; 3-[18F]fluoro-para-hydroxyphenethylguanidine

Eligibility Criteria

Inclusion Criteria

• 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

David M. Raffel, Ph.D.

Research Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David M Raffel, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30558502 (View on PubMed)

Other Identifiers

HUM00088601

Identifier Type: -

Identifier Source: org_study_id