First-in-Human Assessment of Safety, Biodistribution and Pharmacokinetics of 18F-Fluoro-1-Naphthol (18F-4FN) for PET Imaging

18F-4FN represents a novel PET agent for imaging inflammation. Acute inflammatory signaling through the TLR axis recruits neutrophils and macrophages to inflammatory sites. Both cells activate the production of high energy reactive oxygen species/reactive nitrogen species (RONS), setting off a cascade that can be leveraged to detect the presence of these inflammatory cells by molecular imaging. 18F-4FN is efficiently oxidized by high energy RONS, leading to retention and accumulation in human neutrophil-like cells in vitro, and at the sites of acute inflammation in vivo. Like 18F-FDG, 18F-4FN clears rapidly through the kidney at 1 hr following i.v. injection

Study Overview

• Status: Recruiting
• Conditions: Endocrine Neoplasia
• Intervention / Treatment: Drug: 4-[18F]Fluoro-1-Naphthol

Detailed Description

OBJECTIVES:

Primary Objective:

The primary objective of this first-in-human (FIH) study is to determine the safety, biodistribution, and dosimetry profile of a novel positron emission tomography (PET) imaging tracer, 4-[18F]fluoro-1-naphthol ([18F]4FN), which specifically targets reactive oxygen species (ROS). A currently proposed indication for this radiopharmaceutical (RP) is to non-invasively quantify inflammation by PET/CT imaging.

Exploratory Objectives:

One exploratory objective is to identify preliminary efficacy signals from PET/CT images indicating that the new radiopharmaceutical localized to known or clinically-suspected tissues or regions of inflammation mediated by innate immune-related adverse events (irAE). Another exploratory objective is to determine if a time point other than one-hour post injection will yield clinically meaningful improvements to imaging data.

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sanjit Tewari, MD; Phone Number: (832) 729-1874; Email: sotewari@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Sanjit Tewari, MD; Phone Number: 832-729-1874; Email: sotewari@mdanderson.org
      • Principal Investigator: Sanjit Tewari, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient >/= 18 years of age.
• Patients with histologic diagnosis of solid or liquid tumor treated by ICI with evidence of or clinical suspicion of irAE or patients with suspected inflammation.
• Normal range standard renal and liver function tests for age:

eGFR >= 60 mL/min/1.73 m2

Adequate liver function:

Bilirubin ≤ the upper limit of normal (ULN) Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ the ULN

Exclusion Criteria:

• Pregnant or lactating women: pregnant women are excluded from this study because the effects of [18F]4FN in pregnancy are not known. Urine or serum pregnancy test (female </= 60 years of age or childbearing potential) within 24 hours of the PET scan.
• Subjects with contraindications to the use of [18F]4FN including confirmed allergy.
• Patients with a body weight of 400 pounds or more, or a BMI which precludes their entry into the bore of the PET/CT scanner, because the hardware is not intended to support that weight.
• Any additional medical condition, serious concurrent illness, or other extenuating circumstance that, in the opinion of the physician may significantly interfere with study compliance.
• Children below the age of 18 are excluded because of the unknown but potential risk of administration of radiopharmaceuticals to minors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4-[18F]Fluoro-1-Naphthol; Participants will receive 1 injection of [18F]4FN	Drug: 4-[18F]Fluoro-1-Naphthol; By vein (IV); Other Names: [18F]4FN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To identify preliminary efficacy signals from PET images that correlate with clinical foci of ICI-related irAE.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Sanjit Tewari, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2022
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: February 18, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms
• Other Study ID Numbers: 2021-0784; NCI-2022-01722 (Other Identifier: NCI-CTRP-Clinical Trial Reporting Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No