PET Radioligands for Rheumatoid Arthritis

Overseen By Tara N Turon, C.R.N.P.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: NSAIDs, Willow bark tea, Probenecid

Disqualifiers: HIV, Cardiovascular disease, Pregnancy, others

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

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test two new drugs that might enhance PET scans for detecting inflammation in the body. Researchers seek to determine if one of these drugs, called [11C]MC1, can produce clearer images of inflammation, particularly in individuals with rheumatoid arthritis or autoimmune muscle disorders. Participants should either have rheumatoid arthritis, idiopathic inflammatory myopathy (a muscle disease with inflammation), or be healthy volunteers already enrolled in specific studies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that participants stop taking non-steroidal anti-inflammatory drugs (NSAIDs) or willow bark tea for two weeks before the PET scan. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial requires that participants stop taking non-steroidal anti-inflammatory drugs (NSAIDs) or willow bark tea for two weeks before the PET scan. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the two investigational drugs, [11C]MC1 and [11C]ER176, are under study to determine if they can enhance PET scan images of inflammation. These drugs are used in very small amounts to highlight inflammation during imaging, not to treat it.

Currently, limited safety information is available for [11C]MC1 and [11C]ER176 in humans, as this is an early-stage trial. As a Phase 1 trial, the primary goal is to assess the safety of the drugs and their tolerability in people. This phase involves careful monitoring of participants to ensure their safety.

Celecoxib, another drug used in the study, is well-known and FDA-approved for treating pain and inflammation. It is generally well-tolerated, but like any medication, it can cause side effects, such as stomach issues or an increased risk of heart problems in some individuals.

While specific safety data on [11C]MC1 and [11C]ER176 is still being collected, trial participants will be closely monitored to manage any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it is exploring innovative PET radioligands, like 11C-ER176 and 11C-MC1, to better understand inflammatory conditions such as rheumatoid arthritis. Unlike traditional treatments that focus primarily on symptom management, this study aims to visualize inflammation at a molecular level, enhancing our understanding of these conditions. This approach could lead to more precise and personalized treatment strategies. Moreover, by incorporating celecoxib, the trial investigates how blocking certain pathways affects inflammation, potentially paving the way for more effective therapies.

What evidence suggests that this trial's treatments could be effective for imaging inflammation in rheumatoid arthritis?

This trial tests the new radioligands \[11C\]MC1 and \[11C\]ER176 to improve PET scans for detecting inflammation. In this study, \[11C\]MC1 enhances PET images, which is crucial for conditions like rheumatoid arthritis, where inflammation is significant. Similarly, \[11C\]ER176 is evaluated to see if it can also improve PET images for inflammatory conditions. Both radioligands aim to differentiate between types of inflammation, potentially helping doctors better understand and treat these conditions. Early results appear promising, but further research is needed to confirm these findings. ^{1 2 6 7 8}

Who Is on the Research Team?

Robert B Innis, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

Adults over 18 with rheumatoid arthritis or idiopathic inflammatory myopathy (IIM), and healthy adults enrolled in specific protocols, can join this trial. Participants must be able to perform all study procedures and provide consent. Women should not plan to become pregnant soon. NSAIDs use is a disqualifier, along with certain medical conditions.

Inclusion Criteria

I am over 18, can follow the study plan, agree to participate, and if female, not planning to get pregnant soon.

I am an adult with RA, can follow the study plan, and not planning to get pregnant soon.

I am over 18, healthy, can follow the study plan, and if female, not planning to get pregnant soon.

Exclusion Criteria

I haven't taken NSAIDs or willow bark tea for two weeks before a PET scan.

Unable to travel to NIH, recent exposure to radiation related to research, inability to lie flat on camera bed for at least two hours, current pregnancy or breastfeeding, substance use disorder or alcohol use disorder, NIMH employees and staff or immediate family member of NIMH employee/staff.

People with certain medical conditions that prevent them from having an MRI scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Phase 1: Pilot

Healthy participants receive about 10 mCi of [11C]MC1 intravenously followed by a whole body PET/CT scan to measure uptake in ovaries and testes.

1 day

1 visit (in-person)

Phase 2: Whole body PET/CT scans

Participants with RA, IIM, or AxSpA undergo baseline and blocking whole body PET/CT scans using [11C]MC1 and celecoxib.

2 days

2 visits (in-person)

Phase 3: Brain PET/CT scans

RA patients and healthy subjects undergo brain-dedicated PET/CT scans with [11C]MC1 and celecoxib.

1 day

1 visit (in-person)

Phase 4: Follow-up Imaging

RA patients are imaged during moderate to severe symptoms and after clinically-indicated therapy for about two to four months.

2-4 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 11C-ER176
• 11C-MC1
• Celecoxib

Trial Overview The trial tests if two new drugs, [11C]ER176 and [11C]MC1, improve PET scan imaging of inflammation in patients with arthritis or IIM compared to healthy volunteers. It involves taking celecoxib orally, undergoing PET scans, and possibly CT scans or MRIs.

How Is the Trial Designed?

Group I: Phase 3: Brain PET/CT scans in healthy participants Experimental Treatment 3 Interventions

Healthy participants had a baseline brain PET/CT scan after receiving about 20 mCi \[11C\]MC1 followed by a second brain PET/CT scan with 20 mCi \[11C\]MC1 intravenously after blockade with single dose of celecoxib 600 mg orally on same day. Participants had arterial blood sampling with each brain scan.

Group II: Phase 2: Whole body PET/CT scans in patients Experimental Treatment 3 Interventions

Participants with rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM), or axial spondyloarthritis (AXSPA), had a baseline whole body PET/CT scan after about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.

Group III: Phase 2: Whole body PET/CT scans in healthy participants Experimental Treatment 4 Interventions

Healthy participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]MC1 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]MC1 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day. In a second visit, participants had a baseline whole body PET/CT scan after receiving about 15 mCi of \[11C\]ER176 followed by a second whole body PET/CT scan with about 15 mCi of \[11C\]ER176 intravenously after blockade with single dose of celecoxib 200-400 mg orally on same day.

Group IV: Phase 1: Pilot - Whole body scan in health participants Experimental Treatment 2 Interventions

Healthy participants receive about 10 mCi of \[11C\]MC1 intravenously followed by a whole body PET/CT scan. If radiation dose to selected body organs is within safety limit, Phase 2 of study was initiated

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

The synthesized COX-2 inhibitor analogue, 11C-VA426, showed rapid uptake in COX-2 expressing tissues but was highly unstable in vivo, making it unsuitable for PET imaging as a radiopharmaceutical.

Despite initial promising biodistribution results, the compound's rapid washout and instability indicate that further development is needed to enhance its in vivo stability for effective diagnostic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and Preclinical Evaluation of 11C-VA426, a Cyclooxygenase-2 Selective Ligand. Carpinelli, A., Rainone, P., Belloli, S., et al.[2023]

A new iodinated celecoxib analogue, identified as compound 8, shows strong inhibition of COX-2 with very low IC(50) values (0.05 μM against purified COX-2 and 0.03 μM in activated macrophages), indicating its potential as an effective imaging agent for inflammation.

The radiotracer [(123)I]-8 demonstrated high radiochemical yield (85%) and purity (99%), and in vivo SPECT imaging revealed a significant uptake in inflamed tissues, suggesting its efficacy for detecting inflammation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[I]-Celecoxib Analogues as SPECT Tracers of Cyclooxygenase-2 in Inflammation. Uddin, MJ., Crews, BC., Ghebreselasie, K., et al.[2021]

The synthesis of [(11)C]celecoxib, a selective COX-2 inhibitor, was successfully achieved with a high radiochemical yield of 63% and >99% purity, making it a promising PET probe for studying drug transporters.

[(11)C]SC-62807, a major metabolite of celecoxib, was rapidly excreted via hepatobiliary pathways without further metabolism, indicating its potential as an effective PET probe for evaluating drug transporter function in biliary excretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient sequential synthesis of PET Probes of the COX-2 inhibitor [11C]celecoxib and its major metabolite [11C]SC-62807 and in vivo PET evaluation. Takashima-Hirano, M., Takashima, T., Katayama, Y., et al.[2015]

The study demonstrated that [11C]celecoxib, a COX-2 selective inhibitor, effectively penetrates the blood-brain barrier and accumulates in the brain, indicating its potential for monitoring COX-2 activity in neurological conditions.

Radiation dosimetry assessments suggest that the maximum safe dosage of [11C]celecoxib for human studies is 1110 MBq (30 mCi), ensuring safety for research participants while exploring its therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Brain Imaging, Biodistribution, and Radiation Dosimetry Estimation of [11C]Celecoxib, a COX-2 PET Ligand, in Nonhuman Primates. Kumar, JSD., Bai, B., Zanderigo, F., et al.[2018]

A novel method for labeling nonsteroidal anti-inflammatory drugs (NSAIDs) with carbon-11 allows for effective in vivo imaging of cyclooxygenase (COX) activity using positron emission tomography (PET).

MicroPET studies in rats demonstrated that these labeled NSAIDs, particularly [(11)C]Ketoprofen, accumulate in inflamed brain regions, indicating their potential for studying neuroinflammation and COX expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General method for the (11)C-labeling of 2-arylpropionic acids and their esters: construction of a PET tracer library for a study of biological events involved in COXs expression. Takashima-Hirano, M., Shukuri, M., Takashima, T., et al.[2012]

New carbon-11-labeled celecoxib derivatives were successfully developed as potential PET radiotracers for imaging the COX-2 enzyme, which is overexpressed in various cancers, achieving high radiochemical purity (>99%) and yields (52-57%).

In vitro tests showed that these new compounds effectively inhibit COX-2 in cancer cells, with IC(50) values comparable to the well-known COX-2 inhibitor celecoxib, suggesting their potential for further evaluation in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer. Gao, M., Wang, M., Miller, KD., et al.[2016]

The radiolabeled COX-2 inhibitor [11C]MOV was successfully synthesized with high radiochemical purity and yield, allowing for its evaluation in vivo in both rats and baboons.

PET imaging in baboons showed low uptake of [11C]MOV in the brain, indicating rapid metabolism in plasma, while microPET studies in rats demonstrated specific binding in the thorax that could be blocked by the COX-2 inhibitor valdecoxib, suggesting the tracer's potential for studying COX-2 activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and in vivo evaluation of [11C]MOV as a PET imaging agent for COX-2. Prabhakaran, J., Underwood, M., Zanderigo, F., et al.[2019]

Celecoxib, a COX-2 inhibitor, has been shown to be effective in treating osteoarthritis and rheumatoid arthritis, providing significant pain relief and functional improvements within 2 weeks of starting treatment, with effects maintained for up to 24 weeks in clinical trials involving various dosages.

Celecoxib has a better gastrointestinal safety profile compared to traditional NSAIDs, with fewer upper gastrointestinal complications, making it a suitable alternative for patients at higher risk for such issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. Clemett, D., Goa, KL.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03912428

Study Details | NCT03912428 | Novel PET Radioligand as ... Using wholebody imaging, this study seeks to determine whether PET imaging using these new radioligands can differentiate two inflammatory conditions-rheumatoid ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03912428?tab=table

Novel PET Radioligand as an Inflammatory Biomarker in ... Using wholebody imaging, this study seeks to determine whether PET imaging using these new radioligands can differentiate two inflammatory conditions-rheumatoid ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9931986/

[18F] FDG uptake in patients with spondyloarthritis The present study aimed to evaluate correlation if any, between FDG uptake and disease activity as assessed by serum inflammatory biomarker ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT03912428?keyword=%22Inflammatory%22

Novel PET Radioligands as Inflammatory Biomarkers in ... Using wholebody imaging, this study seeks to determine whether PET imaging using these new radioligands can differentiate two inflammatory conditions-rheumatoid ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40310563/

Fibroblast activation protein-targeted PET/CT with 68 Ga ... This study aims to explore the utility of 68 Ga-FAPI-46 PET/CT for assessing active inflammation in axSpA.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03912428?tab=history&a=206

Record History | ver. 206: 2025-03-25 | NCT03912428 Our laboratory recently developed two new radioligands: [11C]ER176 to image TSPO and [11C]MC1 to image COX-2. Using wholebody imaging, this study seeks to ...

7. smartpatients.com smartpatients.com/trials/NCT03912428

Novel PET Radioligand as an Inflammatory Biomarker ... PET scans can help detect inflammation. Two new drugs may create better PET images. Objective: - To see if the drug [11C]MC1 can help image inflammation.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11270841/

Prevalence and location of inflammatory and structural lesions ... Prevalence and location of inflammatory and structural lesions in patients with rheumatoid arthritis and radiographic axial spondyloarthritis ...