Novel PET Radioligand as an Inflammatory Biomarker in Musculoskeletal Conditions

NCT03912428 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 19007919-M-0079
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Inflammation plays a significant role in various disorders that involve neurodegeneration or autoimmune reaction as one of their mechanisms. 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. Eligibility:

• People age 18 and older with rheumatoid arthritis or idiopathic inflammatory myopathy (IIM).
• Healthy volunteers enrolled in protocol 01-M-0254 or 17-M-0181 are also needed. Design:
• Healthy participants will be screened under protocol 01-M-0254 or 17-M-0181.
• Participants with arthritis or IIM will have a screening visit. This will include:
• Medical history
• Physical exam
• Blood and urine tests
• Possible CT or X-ray: A machine will take pictures of the body.
• Healthy participants will have 1 or 2 visits. They may have urine tests. They may take the drug celecoxib by mouth. They will have a PET scan. A small amount of one or both study drugs will be injected through a catheter: A needle will guide a thin plastic tube into an arm vein. Another catheter will draw blood. They will like on a bed that slides into a machine. Their vital signs and heart activity will be measured.
• Participants with arthritis will have up to 2 visits after screening. They may take celecoxib and have PET scans.
• Participants with IIM will have up to 3 visits after screening. At 1 or 2 visits, they will take celecoxib and have PET scans. They will have 1 visit where they have an MRI: They will lie on a table that slides into a machine. The machine takes pictures of the body.

Conditions

Myositis; Inflammatory; Rheumatoid Arthritis; Healthy Volunteers

Keywords

Inflammatory; PET Imaging

Outcome Measures

Primary Outcomes (7)

• Uptake of [11C]MC1 by Organs

  Participant received whole body PET/CT scan and radioligand uptake of \[11C\]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.

  Up to 120 minutes during each scan

• Uptake of [11C]MC1 by Organs - Gender Specific Organs

  Participant received whole body PET/CT scan and radioligand uptake of \[11C\]MC1 in selected body regions of interest was quantified as a Standardized Uptake Value (SUV) using the Siemens Biograph Micro-Computed Tomography (mCT) with an injected dose of 9 mCi. Organ dosimetry was measured as dose per organ in Roentgen Equivalent Man (rem), which is absorbed dose times an organ-specific quality factor.

  Up to 120 minutes during each scan

• Phase 2: [11C]MC1 Binding in Inflamed Body Parts - HANDS

  The uptake of \[11C\]MC1 before (baseline) and after blockade by single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

  Up to 120 minutes during each scan

• Phase 2: [11C]MC1 Binding in Non-inflamed Body Parts - HANDS

  The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

  Up to 120 minutes during each scan

• Phase 2: [11C]MC1 Binding in Inflamed Body Parts - KNEES

  The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in inflamed regions of the body in patients. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

  Up to 120 minutes during each scan

• Phase 2: [11C]MC1 Binding Between Non-inflamed Body - KNEES

  The uptake of \[11C\]MC1 before (baseline) and after blockade by a single dose of celecoxib 400mg orally in non-inflamed regions of the body in healthy participants. The radioligand uptake of \[11C\]MC1 during whole body PET/CT scans in selected regions of interest was quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight, using Bruker's PMOD quantification software.

  Up to 120 minutes during each scan

• Whole Brain Volume of Distribution (VT)/ Free-fraction (fP) of [11C]MC1

  The volume of distribution (VT) of \[11C\]MC1 measured as the brain-to-plasma ratio using the 2-tissue compartmental modeling divided by free-fraction in the plasma of parent radioligand (fP) at baseline and two hours after blockade with single dose of 600 mg celecoxib orally.

  Up to 120 minutes during each scan

Study Arms (4)

Phase 1: Pilot - Whole body scan in health participants

OTHER

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

Drug: 11C-MC1; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan

Phase 2: Whole body PET/CT scans in patients

OTHER

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.

Drug: 11C-MC1; Drug: Celecoxib; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan

Phase 2: Whole body PET/CT scans in healthy participants

OTHER

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.

Drug: 11C-MC1; Drug: Celecoxib; Drug: [11C]ER176; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan

Phase 3: Brain PET/CT scans in healthy participants

OTHER

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.

Drug: 11C-MC1; Drug: Celecoxib; Diagnostic Test: Positron Emission Tomography (PET)/computed tomography (CT) Scan

Interventions

11C-MC1 DRUG

PET radioligand for Cyclooxygenase-2 (COX-2)

Phase 1: Pilot - Whole body scan in health participants; Phase 2: Whole body PET/CT scans in healthy participants; Phase 2: Whole body PET/CT scans in patients; Phase 3: Brain PET/CT scans in healthy participants

Celecoxib DRUG

Cyclooxygenase-2 (COX-2) inhibitor

Also known as: Celebrex

Phase 2: Whole body PET/CT scans in healthy participants; Phase 2: Whole body PET/CT scans in patients; Phase 3: Brain PET/CT scans in healthy participants

[11C]ER176 DRUG

Radioligand for 18-kDa Translocator Protein

Phase 2: Whole body PET/CT scans in healthy participants

Positron Emission Tomography (PET)/computed tomography (CT) Scan DIAGNOSTIC_TEST

Whole body or brain PET/CT scans

Phase 1: Pilot - Whole body scan in health participants; Phase 2: Whole body PET/CT scans in healthy participants; Phase 2: Whole body PET/CT scans in patients; Phase 3: Brain PET/CT scans in healthy participants

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects
• Aged 18 years or older.
• Willing and able to complete all study procedures.
• Able to provide informed consent.
• Healthy based on medical history, physical examination, and laboratory testing.
• Enrolled in protocol 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers or 17-M-0181 Recruitment and Characterization of Healthy Research Volunteers for National Institute of Mental Health (NIMH) Intramural Studies.
• Be age and sex-matched with patient groups for the 15 subjects in the Phase 2.
• RA patients
• Aged 18 years or older.
• Willing and able to complete all study procedures.
• Able to provide informed consent.
• Have been given a diagnosis of RA based on the published criteria (Aletaha et al., 2010).
• Have moderate to severe symptoms, as defined by a Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) score \>3.2, but RA patients may be in remission for the repeat scan in phase 4.
• IIM patients
• Aged 18 years or older

You may not qualify if:

• Common for all participants
• Because non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX-2, subjects should not have taken NSAIDs or willow bark tea for two weeks prior to the PET scan.
• For Phase 2, 3 and 4 \*contraindications to taking COX-2 inhibitors that, in the opinion of the investigators, have the potential to affect the results or the safety of the participant.
• These may include:
• History of hypersensitivity reaction to COX inhibitors or History of aspirin- or NSAID-induced asthma
• History of upper or lower gastrointestinal bleeding, gastritis, peptic ulcer disease
• History of uncontrolled gastroesophageal reflux disease (GERD), but not medically controlled GERD
• Coagulation disorder
• Thrombocytopenia
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• History of gout
• History of hepatic or renal impairment
• History of cardiovascular disease or presence of cardiovascular risk factors such as uncontrolled or poorly controlled hypertension
• Current use of probenecid
• Patients clinically in remission or who have low disease activity

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (7)

• Ikawa M, Lohith TG, Shrestha S, Telu S, Zoghbi SS, Castellano S, Taliani S, Da Settimo F, Fujita M, Pike VW, Innis RB; Biomarkers Consortium Radioligand Project Team. 11C-ER176, a Radioligand for 18-kDa Translocator Protein, Has Adequate Sensitivity to Robustly Image All Three Affinity Genotypes in Human Brain. J Nucl Med. 2017 Feb;58(2):320-325. doi: 10.2967/jnumed.116.178996. Epub 2016 Nov 17.

  PMID: 27856631 BACKGROUND

• Kreisl WC, Jenko KJ, Hines CS, Lyoo CH, Corona W, Morse CL, Zoghbi SS, Hyde T, Kleinman JE, Pike VW, McMahon FJ, Innis RB; Biomarkers Consortium PET Radioligand Project Team. A genetic polymorphism for translocator protein 18 kDa affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab. 2013 Jan;33(1):53-8. doi: 10.1038/jcbfm.2012.131. Epub 2012 Sep 12.

  PMID: 22968319 BACKGROUND

• van der Laken CJ, Elzinga EH, Kropholler MA, Molthoff CF, van der Heijden JW, Maruyama K, Boellaard R, Dijkmans BA, Lammertsma AA, Voskuyl AE. Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum. 2008 Nov;58(11):3350-5. doi: 10.1002/art.23955.

  PMID: 18975347 BACKGROUND

• Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81. doi: 10.1002/art.27584.

  PMID: 20872595 BACKGROUND

• Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. doi: 10.1056/NEJM197502132920706. No abstract available.

  PMID: 1090839 BACKGROUND

• Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403-7. doi: 10.1056/NEJM197502202920807. No abstract available.

  PMID: 1089199 BACKGROUND

• Shrestha S, Kim MJ, Eldridge M, Lehmann ML, Frankland M, Liow JS, Yu ZX, Cortes-Salva M, Telu S, Henter ID, Gallagher E, Lee JH, Fredericks JM, Poffenberger C, Tye G, Ruiz-Perdomo Y, Anaya FJ, Montero Santamaria JA, Gladding RL, Zoghbi SS, Fujita M, Katz JD, Pike VW, Innis RB. PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study. J Neuroinflammation. 2020 May 2;17(1):140. doi: 10.1186/s12974-020-01804-6.

  PMID: 32359360 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myositis; Arthritis, Rheumatoid

Interventions

(11C)-MC1; Celecoxib; Positron-Emission Tomography; Radionuclide Imaging

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Image Enhancement; Photography; Tomography; Diagnostic Techniques, Radioisotope

Results Point of Contact

• Title: Dr. Robert Innis
• Organization: National Institute of Mental Health

robert.innis@nih.gov

+1 301 594 1368

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 11, 2019
• Study Start: June 14, 2019
• Primary Completion: June 14, 2024
• Study Completion: June 14, 2024
• Last Updated: September 16, 2025
• Results First Posted: September 16, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 18 months after study closure
• Access Criteria: De-identified data can be accessed through NIH Biomedical Translational Research Information System (BTRIS)

Locations

US (1)