[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

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial involves giving a small amount of a new drug called [11C]-NOP46 to people with long-term pain. The drug travels to the painful areas in the body, and a camera takes pictures of these areas. This could help doctors better understand and treat long-term pain.

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 If you can't, you may be withdrawn or rescheduled.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 If you take pain medication within this time, you may be withdrawn from the study or rescheduled.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 safety data exists for [11C]-NOP46 PET/CT scans for chronic pain?

The safety data for [11C]-NOP46, also known as (11)C-NOP-1A, primarily comes from studies on its use as a PET radioligand for imaging nociceptin/orphanin FQ peptide (NOP) receptors. Research has been conducted in both rhesus monkeys and humans to assess its ability to quantify NOP receptors and estimate its radiation safety profile. These studies indicate that (11)C-NOP-1A has a high affinity for NOP receptors and an appropriate safety profile for use in brain imaging. However, specific safety data for its use in chronic pain treatment is not directly addressed in the provided research. ^{1 2 3 4 5}

Is the [11C]-NOP46 PET/CT scan safe for humans?

Research on a similar compound, (11)C-NOP-1A, used for imaging in humans, suggests it has a safe radiation profile based on studies in both monkeys and humans. ^{1 2 3 4 5}

Is the drug [11C]-NOP46 a promising treatment for chronic pain?

Yes, the drug [11C]-NOP46 shows promise as a treatment for chronic pain. It targets a new type of opioid receptor, which is important in managing pain. The drug has been successfully used in brain imaging to study these receptors, which could help in understanding and treating pain more effectively. ^{2 4 6 7 8}

How does the [11C]-NOP46 PET/CT Scan treatment for chronic pain differ from other treatments?

The [11C]-NOP46 PET/CT Scan is unique because it uses a PET imaging technique to visualize the nociceptin/orphanin FQ peptide (NOP) receptors in the brain, which are a new class of opioid receptors potentially involved in pain. This approach is different from traditional pain treatments as it focuses on identifying specific brain receptor activity, which could lead to more targeted and personalized pain management strategies. ^{2 4 6 7 8}

What data supports the idea that [11C]-NOP46 PET/CT Scan for Chronic Pain is an effective treatment?

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 different imaging agents and conditions, such as cancer detection and personalized radiopharmaceuticals, but do not address chronic pain or the specific treatment in question. ^{9 10 11 12 13}

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. Germany 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. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Pre-clinical evaluation of immunoPET imaging using agonist CD40 monoclonal antibody in pancreatic tumor-bearing mice. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer. [2018]

4. United States 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. [2023]

5. Poland pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2022]

7. United States 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of radioligands for imaging brain nociceptin/orphanin FQ peptide (NOP) receptors with positron emission tomography. [2023]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

PET imaging of opioid receptors in pain: progress and new directions. [2019]

10. England 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. [2023]

11. United States 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. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Imaging as a Pain Biomarker. [2022]

13. United States 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. [2022]