[11C]-NOP46 PET/CT Scan for Chronic Pain

Overseen By Akiva Mintz, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Columbia University

Must not be taking: Pain medications, Illicit drugs

Disqualifiers: Diffuse pain, Severe disease, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to understand chronic pain using a special imaging scan (PET/CT) with a tracer called [11C]-NOP46. The goal is to observe how this tracer spreads in the body and to assess its safety. Initially, healthy volunteers participate to ensure safety, followed by patients with moderate to severe pain from a specific injury. Suitable candidates are those experiencing ongoing, intense pain from a specific injury and are under a doctor's care. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to experience this innovative approach.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking pain medications 48 hours before the agent administration. If you can't, you may be withdrawn or rescheduled. Other medications may also be restricted if deemed inappropriate by the investigator.

Will I have to stop taking my current medications?

Yes, you will need to stop taking pain medications for 48 hours before the study agent is given. If you take pain medication within this time, you may be withdrawn from the study or rescheduled.

What prior data suggests that this radiotracer is safe for humans?

Research shows that [11C]-NOP46 is being tested for safety as part of a new imaging method. In earlier studies, this compound helped doctors visualize specific areas of the brain. These studies found that [11C]-NOP46 is generally safe when administered in very small amounts, called microdoses.

In this trial, healthy volunteers will first receive a microdose to check for any side effects. If no harmful effects occur, the trial will proceed with participants who have chronic pain. Using microdoses reduces potential risks. This careful approach suggests that [11C]-NOP46 might be safe in these small amounts, but more testing is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the [11C]-NOP46 PET/CT scan for chronic pain because it offers a new way to visualize pain mechanisms in the body. Unlike standard pain treatments that primarily focus on symptom relief, [11C]-NOP46 targets and highlights specific pain pathways using a novel radioligand. This innovative approach could lead to a better understanding of chronic pain and pave the way for more precise and personalized treatments. By providing detailed imaging of pain processes, this trial could revolutionize how chronic pain is diagnosed and managed.

What evidence suggests that this PET/CT scan is effective for chronic pain?

Research has shown that [11C]-NOP46 is a new imaging tool under study to identify the sources of chronic pain in the body. However, no evidence currently supports its direct use in treating chronic pain. In this trial, participants will receive a microdose of [11C]-NOP46 and undergo PET/CT scans. The primary goal is to scan and understand pain mechanisms in the body. This could help doctors better target treatments in the future. Early results from similar imaging tools have identified pain sources in patients, leading to more effective treatments, but specific results for [11C]-NOP46 remain under investigation. ^{1 2 6 7 8}

Who Is on the Research Team?

Akiva Mintz, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults who can consent to participate. Healthy volunteers must not have chronic pain or be pregnant, and agree to use contraception. Patients with focal pain should experience moderate to severe pain (>4 on the Visual Analogue Scale) and also agree to contraceptive measures.

Inclusion Criteria

I agree to use birth control or abstain from sex during the study.

I am currently experiencing pain from a specific injury and am seeing a doctor for it.

I am a volunteer without any ongoing pain from an injury.

Exclusion Criteria

Concomitant medication use (including suspected illicit drugs use) that, in the judgment of the investigator, would make the participant inappropriate for enrollment.

I do not have widespread pain currently.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Healthy Volunteers

Five healthy volunteers receive a microdose of [11C]-NOP46 and undergo serial whole body PET/CT scans for up to 240 minutes to evaluate biodistribution and derive dosimetry estimates.

1 day

1 visit (in-person)

Stage 2: Individuals with Focal Pain

Up to 30 subjects with focal pain receive a microdose of [11C]-NOP46 and undergo PET/CT scans for up to 60 minutes to determine scanning parameters.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for physiologic effects and uptake ratio for 48 hours post-scan.

48 hours

What Are the Treatments Tested in This Trial?

Interventions

• [11C]-NOP46

Trial Overview The study tests a new radiotracer called [11C]-NOP46 using PET/CT scans in two stages: first in five healthy individuals for safety, then in thirty patients with chronic pain if no toxicities are found.

How Is the Trial Designed?

Group I: Individuals with Focal Pain Experimental Treatment 2 Interventions

In Stage 2, up to 30 subjects with focal pain will receive a microdose of \[11C\]-NOP46 and undergo PET/CT scans for up to 60 minutes in length. The results of Stage 1 will inform the scanning parameters (uptake period, scan length, reconstruction parameters, etc.) for Stage 2.

Group II: Healthy Volunteers Experimental Treatment 2 Interventions

In Stage 1, five healthy volunteers will receive a microdose of \[11C\]-NOP46 and undergo serial whole body PET/CT scans for up to 240 minutes post-administration. These image sets will be used to evaluate \[11C\]-NOP46 biodistribution and derive dosimetry estimates.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Akiva Mintz

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

Recent advancements in PET imaging allow researchers to visualize opioid receptors in humans during pain, enhancing our understanding of how these receptors function in pain management.

Changes in mu opioid receptor occupancy have been observed in response to experimental pain, suggesting that this imaging technique could lead to new insights and clinical applications for treating pain syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging of opioid receptors in pain: progress and new directions. Ravert, HT., Bencherif, B., Madar, I., et al.[2019]

The novel [64Cu]Cu-NOTA-aCD40 immunoPET tracer showed significantly higher accumulation in pancreatic tumors compared to a control tracer, indicating its specificity for targeting CD40+ tumors in a mouse model.

Safety assessments for human imaging with [64Cu]Cu indicated a favorable organ dose profile, particularly with a lower injected mass, suggesting it could be a safe option for imaging in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical evaluation of immunoPET imaging using agonist CD40 monoclonal antibody in pancreatic tumor-bearing mice. Aghevlian, S., Wu, B., Raie, MN., et al.[2022]

A 64Cu-labeled antibody targeting CD146 was developed and successfully used for PET imaging in six lung cancer models, showing a strong correlation between CD146 expression and tumor uptake of the radiotracer.

The highest tumor uptake of the radiotracer was observed in lung cancer models with high CD146 expression, indicating its potential for monitoring tumor progression and tailoring treatment strategies based on CD146 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer. Sun, H., England, CG., Hernandez, R., et al.[2018]

The study of 124I-labeled toripalimab (124I-JS001) in 11 patients with melanoma and urologic cancer showed it to be a safe PET imaging tracer with no adverse events and acceptable dosimetry of 0.236 mSv/MBq.

124I-JS001 demonstrated favorable biodistribution, with high uptake in the spleen and liver, and significantly improved tumor detection when combined with unlabeled JS001, indicating its potential as a tool for identifying patients who may benefit from PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron Emission Tomography Imaging of Programmed Death 1 Expression in Cancer Patients Using 124I-Labeled Toripalimab: A Pilot Clinical Translation Study. Wang, S., Zhu, H., Ding, J., et al.[2023]

There is increasing interest in finding objective biomarkers for chronic pain, especially in light of the opioid crisis and the need for better pain management strategies.

Neuroimaging studies suggest that chronic pain is linked to specific changes in brain regions and networks, which could serve as unique biomarkers to improve diagnosis and treatment of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging as a Pain Biomarker. Kashanian, A., Tsolaki, E., Caruso, J., et al.[2022]

In a rodent model of cancer-induced bone pain, treatment with nociceptin and the NOP receptor agonist Ro65-6570 significantly reduced pain-related behaviors, indicating their potential as effective analgesics.

The study found that the NOP receptor system could be a promising target for treating cancer-induced bone pain, as evidenced by the dose-dependent reversal of pain-like behaviors in the treated animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nociceptin/orphanin FQ receptor system as a target to alleviate cancer-induced bone pain in rats: Model validation and pharmacological evaluation. Sliepen, SHJ., Korioth, J., Christoph, T., et al.[2023]

A new PET radioligand, [(11)C]-(S)-30, has been developed to effectively visualize the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor in the brain, showing promising results in both rat and monkey studies.

This radioligand demonstrated excellent brain uptake and minimal production of unwanted metabolites, making it a strong candidate for future human clinical studies to better understand the role of the NOP receptor in neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor. Pedregal, C., Joshi, EM., Toledo, MA., et al.[2022]

The new radioligand (11)C-NOP-1A shows high affinity for the nociceptin/orphanin FQ peptide (NOP) receptor and is effective for PET brain imaging, demonstrating specific binding in the monkey brain with a peak uptake occurring around 12 minutes post-injection.

The estimated radiation dose for humans from (11)C-NOP-1A is 5.0 μSv/MBq, which is comparable to other (11)C-labeled neuroreceptor ligands, indicating a favorable safety profile for potential use in human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain and whole-body imaging in rhesus monkeys of 11C-NOP-1A, a promising PET radioligand for nociceptin/orphanin FQ peptide receptors. Kimura, Y., Fujita, M., Hong, J., et al.[2022]

The radioligand (11)C-NOP-1A effectively quantifies NOP receptors in the human brain, showing high peak concentrations and stable measurements, which suggests its potential for studying anxiety and drug abuse disorders.

The radiation exposure from (11)C-NOP-1A is low, with an effective dose of 4.3 μSv/MBq, making it safe for multiple scans in a single subject, similar to other (11)C-labeled radioligands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain and whole-body imaging of nociceptin/orphanin FQ peptide receptor in humans using the PET ligand 11C-NOP-1A. Lohith, TG., Zoghbi, SS., Morse, CL., et al.[2023]

The novel PET ligand [(11)C]NOP-1A shows high uptake in the brain, indicating its potential for effectively imaging nociceptin/orphanin FQ peptide (NOP) receptors, with peak concentrations observed in regions like the putamen and cingulate cortex.

The study demonstrated that [(11)C]NOP-1A has moderately good reproducibility and reliability in measuring receptor density (VT) across various brain regions, making it a valuable tool for comparing NOP receptor binding in different populations or conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retest imaging of [11C]NOP-1A binding to nociceptin/orphanin FQ peptide (NOP) receptors in the brain of healthy humans. Lohith, TG., Zoghbi, SS., Morse, CL., et al.[2023]

A new PET radioligand, [(11)C](S)-10c, was developed to study NOP receptors in the brain, showing high receptor-specific binding and favorable kinetics in monkey studies.

This radioligand could help explore the connections between neuropsychiatric disorders and NOP receptors, with plans for evaluation in human subjects following promising results in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of radioligands for imaging brain nociceptin/orphanin FQ peptide (NOP) receptors with positron emission tomography. Pike, VW., Rash, KS., Chen, Z., et al.[2023]

The study developed a targeted imaging agent, CD166tp-G18C, which effectively binds to colorectal cancer stem cells (CRCSCs) in a mouse model, indicating its potential for detecting these cells in cancer therapy.

Using indium-111 to label the CD166tp-G18C probe, researchers found significantly enhanced imaging in tumor tissues, suggesting that this method could improve the detection and monitoring of colorectal cancer stem cells in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model. Guan, SS., Wu, CT., Liao, TZ., et al.[2020]

A new method for modifying 2-[18F]FDG was developed using bifunctional tetrazines, allowing for personalized radiopharmaceuticals that can be synthesized in standard clinical settings.

The modification process achieved high radiochemical yields (70-99%) and can facilitate bioorthogonal strategies for targeted therapies, enhancing the precision of diagnosis and treatment in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An approach to develop personalized radiopharmaceuticals by modifying 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG). Simeonova, G., Todorov, B.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03705819

NCT03705819 | Exploratory Evaluation of [11C]-NOP46 In Stage 2, up to 30 subjects with focal pain will receive a microdose of [11C]-NOP46 and undergo PET/CT scans for up to 60 minutes in length. The results of ...

2. withpower.com withpower.com/trial/early-phase-1-chronic-pain-2-2019-ec0bc

[11C]-NOP46 PET/CT Scan for Chronic Pain The available research does not provide any data supporting the effectiveness of [11C]-NOP46 PET/CT Scan for Chronic Pain. The studies mentioned focus on ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11493400/

Imaging of Pain using Positron Emission Tomography - PMC This review covers the most important PET tracers that have been used to image pain including tracers for fundamental biological processes.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03195270

NCT03195270 | Use of PET/MR Imaging in Chronic Pain Data from chronic pain patients will be compared to historical data from asymptomatic controls. Masking : None (Open Label). Arms and Interventions ...

5. auntminnie.com auntminnie.com/clinical-news/molecular-imaging/article/15677645/new-pet-tracer-visualizes-drivers-of-chronic-pain

New PET tracer visualizes drivers of chronic pain A recently developed PET radiotracer identified sources of pain in patients with complex regional pain syndrome (CRPS) and led to effective treatments.

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03705819/exploratory-evaluation-of-11c-nop46

Exploratory Evaluation of [11C]-NOP46 This is an open-label, single center design. In the first stage, five (5) healthy individuals will receive a microdose (10µg) of [11C]-NOP46 ...

7. bioworld.com bioworld.com/articles/670994-columbia-university-conducts-exploratory-evaluation-of-11c-nop46-pet-tracer-for-chronic-pain

NOP46 PET tracer for chronic pain If no toxicities develop, then the investigation will move to the second stage, in which 30 patients with chronic pain will receive a microdose ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22795050/

pooled analysis of 11 clinical studies Objectives: The objective of this analysis was to assess the pooled safety data of OROS hydromorphone ER in opioid-tolerant patients with chronic cancer and ...