PET Imaging with FNP-59

Overseen By Benjamin L Viglianti, M.D, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Benjamin Viglianti

Must not be taking: Steroids, OCP, ACE inhibitors, others

Disqualifiers: Pregnancy, Adrenal pathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for imaging the adrenal gland using a special agent called [18F]FNP-59 (also known as Fluorinated NP-59 or [18F]3OAc-FNP-59). The goal is to determine if small doses of this agent can effectively display adrenal gland activity. Some participants will have their hormone levels altered with medications like dexamethasone or cosyntropin to observe changes in imaging. Healthy individuals without adrenal issues and not on certain medications might qualify for some groups, while those with known adrenal gland problems could join another group. As an Early Phase 1 trial, this research aims to understand how this new imaging agent works in people, offering participants the chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

Yes, if you are in Groups 2 or 3, you must stop taking steroids, oral contraceptives, spironolactone, estrogen, androgen, progesterone, ACE inhibitors, ARBs, or hormone-like supplements.

What prior data suggests that this imaging technique is safe for humans?

Research has shown that [18F]FNP-59, a new imaging agent, is safer than older versions. Early studies suggest it functions like previous agents but with an improved safety profile. This agent, containing fluorine-18, aids doctors in visualizing the adrenal glands. Although data remains limited, this research phase focuses on patient tolerance. As an early trial, the primary goal is to identify any side effects and ensure safety for further testing. The results so far are promising, but additional research is needed to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the PET imaging trial with [18F]FNP-59 because it offers a unique approach to understanding adrenal gland conditions. Unlike traditional imaging methods, [18F]FNP-59 targets specific receptor sites, potentially providing more detailed and accurate imaging of adrenal activity. This could lead to better diagnosis and treatment plans. The trial explores various scenarios, such as using dexamethasone to suppress cortisol production and cosyntropin to stimulate adrenal function, offering insights into how adrenal glands respond to these interventions. This novel imaging technique might pave the way for more precise assessments compared to standard CT or MRI scans.

What evidence suggests that this trial's imaging techniques could be effective for adrenal gland evaluation?

Research has shown that [18F]FNP-59 is a promising tool for imaging the adrenal glands. This substance, similar to a type of cholesterol, enhances PET scan images. Early studies suggest that [18F]FNP-59 can highlight adrenal activity, aiding in the detection of problems. In this trial, participants will be divided into groups to assess the effectiveness of [18F]FNP-59 under various conditions, such as with Dexamethasone or Cosyntropin. The goal is to obtain clearer images of the adrenal glands, potentially leading to more accurate diagnoses. Although its full effectiveness in humans is still under investigation, initial results are promising for improved PET scan images of adrenal conditions. ^{2 3 4 6 7}

Who Is on the Research Team?

Benjamin L Viglianti, M.D, Ph.D.

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for healthy individuals without adrenal gland issues, who will undergo hormone manipulation, or those with abnormal adrenal hormone secretion. It's not for pregnant women, prisoners, people over 400 lbs, steroid users, or those on certain medications like OCPs and ACE inhibitors.

Inclusion Criteria

My adrenal glands are healthy and I have not been diagnosed with any adrenal diseases.

You have abnormal hormone levels from your adrenal glands.

Exclusion Criteria

Pregnancy

Prisoners are not eligible

I can give my own consent to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Imaging and Hormone Manipulation

Participants undergo an initial FNP-59 scan and hormone manipulation (dexamethasone or cosyntropin) for Groups 2 and 3.

4 days

2 visits (in-person)

Follow-up Imaging

Participants undergo follow-up FNP-59 scans to assess changes in uptake.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18F]FNP-59

Trial Overview The study tests a new PET/CT scan using [18F]FNP-59 to image the adrenal gland. Some participants will also receive Cosyntropin (Group 3) or Dexamethasone (Group 2) to see how these drugs affect imaging results.

How Is the Trial Designed?

Group I: Dexamethasone (Group 2) Experimental Treatment 2 Interventions

Participants will undergo an FNP-59 scan on day 0 in the am. Participants will then take 1 mg dexamethasone 2x a day for 3 days to suppress cortisol production. Participants will then have a second FNP-59 scan on day 4 in the am.

Group II: Cosyntropin (Group 3) Experimental Treatment 2 Interventions

Participants will undergo an FNP-59 scan on day 0 in the am. On day 4 the participant will arrive for imaging. Cosyntropin, 250 micro-gm will be administered IV. Five minutes following administration FNP-59 will be given. Following uptake of FNP-59 imaging will occur.

Group III: Adrenal pathology (Group 4) Experimental Treatment 1 Intervention

Whole-body PET/CT scans will be done on 4 patients at 1 hr and the other 4 patients at 6 hours. All the patients will have a whole-body PET/CT scan at 3 hours.

Who Is Running the Clinical Trial?

Benjamin Viglianti

Lead Sponsor

Trials

2

Recruited

30+

Published Research Related to This Trial

Fluorodeoxyglucose (FDG) is a widely used PET imaging agent for cancer detection, but it can produce false positive and false negative results in certain clinical situations.

Research is ongoing to develop new PET tracers, particularly fluorinated compounds, to improve accuracy in cancer imaging and potentially replace FDG in specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond FDG: novel PET tracers for cancer imaging. Hicks, RJ.[2021]

18F-labeled PSMA-targeted PET imaging agents for prostate cancer offer significant advantages over traditional 68Ga-labeled compounds, including better availability in smaller hospitals and potential cost savings due to easier distribution.

These 18F-labeled compounds provide improved image quality with higher positron yield and lower noise, enhancing the detection of subtle lesions and allowing for more flexible imaging protocols, which may lead to better diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging. Werner, RA., Derlin, T., Lapa, C., et al.[2023]

FDG is currently the only fluorinated tracer used in clinical PET imaging, providing high-resolution images due to its ideal properties, including low positron energy and a suitable half-life for dynamic studies.

Recent advancements in the synthesis of fluorinated tracers, particularly using prosthetic group precursors, have led to the development of both generalist and specific tracers that may enhance PET imaging in cancer patients, potentially expanding beyond the capabilities of FDG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorinated tracers for imaging cancer with positron emission tomography. Couturier, O., Luxen, A., Chatal, JF., et al.[2018]

The automated synthesis method for the imaging agent [18F]FEPPA yielded a high radiochemical yield of 38% and met U.S. Pharmacopoeia quality standards, making it suitable for clinical and preclinical studies.

MicroPET imaging demonstrated that [18F]FEPPA effectively highlighted increased neuroinflammation in the brains of rats exposed to fine particulate matter (PM2.5), indicating its potential as a tracer for studying neuroinflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroinflammation in Low-Level PM2.5-Exposed Rats Illustrated by PET via an Improved Automated Produced [18F]FEPPA: A Feasibility Study. Cheng, MF., Cheng, TJ., Guo, YL., et al.[2022]

The synthesized compound 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (FENP) shows high affinity for the progesterone receptor and can be produced in a two-step synthesis with a yield of 4-30% within 40 minutes after [18F]fluoride ion production.

In vivo studies in estrogen-primed rats reveal that [18F]FENP has highly selective uptake in the uterus, indicating its potential for imaging progestin target tissues and receptor-rich tumors, such as breast tumors, using positron emission tomography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography. Pomper, MG., Katzenellenbogen, JA., Welch, MJ., et al.[2019]

The PET ligands (18)F-FEAC and (18)F-FEDAC effectively visualize translocator protein (TSPO) expression in the infarcted rat brain, indicating their potential for studying brain injuries.

Both ligands showed favorable kinetics in the monkey brain, with minimal metabolism during PET scans, suggesting they could be useful for imaging TSPO in primates and possibly in human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FEAC and 18F-FEDAC: PET of the monkey brain and imaging of translocator protein (18 kDa) in the infarcted rat brain. Yui, J., Maeda, J., Kumata, K., et al.[2016]

The automated production method for no-carrier-added (NCA) [18F]FDOPA achieved a decay-corrected radiochemical yield of 10-14% over 7 trials, with a synthesis time of approximately 110 minutes.

The synthesized [18F]FDOPA demonstrated over 95% radiochemical purity and a high molar activity of around 431 GBq/μmol, indicating its potential for effective use in medical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-step two-pot automated production of NCA [18F]FDOPA with FlexLab module. Huang, YY., Poniger, S., Tsai, CL., et al.[2020]

The synthetic procedure for [18F]FPCBT, an imaging agent for the dopamine transporter, produced a radiochemical purity of over 96%, yielding enough product (20 to 30 mCi) for two to three studies.

In vivo studies in baboons showed that [18F]FPCBT has good brain uptake, with peak striatal uptake occurring within 7 to 10 minutes post-injection, indicating its potential as an effective candidate for dopamine transporter imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis of [18F] N-(3-Fluoropropyl)-2-beta-Carbomethoxy-3-beta-(4-Bromophenyl) Nortropane and the regional brain uptake in non human primate using PET. Chaly, T., Baldwin, RM., Neumeyer, JL., et al.[2019]

Positron emission tomography/computed tomography (PET/CT) is a rapidly growing imaging technique in cancer management, but the commonly used radiotracer [(18)F]fluorodeoxyglucose (FDG) is not specific for malignant disease, highlighting the need for more tumor-specific PET radiopharmaceuticals.

Over the past 15 years, various alternative (18)F-labeled radiotracers have been developed and evaluated, which may provide better characterization of tumor biology, emphasizing the importance of regulatory compliance and safety in their clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. Vallabhajosula, S.[2022]

Positron emission tomography (PET) is a rapidly advancing imaging technique that allows for noninvasive visualization and measurement of biological processes in cancer patients, enhancing clinical management.

While the widely used [(18)F]FDG-PET is effective for various cancer assessments, the development of target-specific PET tracers over the past decade offers more precise insights into cancer biology and progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography imaging of cancer biology: current status and future prospects. Chen, K., Chen, X.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35483964/

Development of Fluorinated NP-59: A Revival of Cholesterol ... The goal of this study was to prepare and evaluate a 18 F analog of NP-59 to serve as a PET imaging agent for functional imaging of the adrenal glands based on ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04546126?tab=table

Clinical Evaluation of [18F]FNP-59 in Normal Human ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04532489/positron-emission-tomography-pet-imaging-of-cholesterol-trafficking-clinical-evaluation-of-18ffnp-59-in-normal-human-subjects-group-1

Clinical Evaluation of [18F]FNP-59 in Normal Human ... The researchers believe that [18F]FNP-59 would greatly improve the imaging characteristics, by providing a PET imaging cholesterol analogue with ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT04546126?keyword=%22Cholesterol%22

Clinical Evaluation of [18F]FNP-59 in Normal Human ... ... PET/CT scans.~The researchers believe that a fluorine-18 analogue of NP-59, \[18F\]FNP-59, would greatly improve the imaging characteristics, by providing a PET ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11317997/

3AcFNP-59 for Positron Emission Tomography Imaging ... The biodistribution data demonstrated faster adrenal uptake for the ester radiotracers than [18F]FNP-59, indicating better association with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9730927/

Development of Fluorinated NP-59: A Revival of Cholesterol ... The preliminary evaluation demonstrated that 18F-FNP-59 behaved in a manner nearly identical to historic 131I-NP-59 data, with a greatly improved safety profile ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07110519

Study Details | NCT07110519 | Positron Emission ... This is a Phase 0 interventional, non-therapeutic study investigating the biodistribution and safety of [18F]-fluoromannitol as a radiotracer (a substance used ...