Brain Imaging Tracer for Neurodegenerative Disease

Overseen By Rodolfo Arevalo, BA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Columbia University

Must not be taking: Investigational radiation drugs

Disqualifiers: Brain disease, 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 aims to test a new brain imaging tracer called [11C]MPC6827, which could help detect neurodegenerative diseases like Alzheimer's and ALS. Researchers seek to understand how this tracer spreads in the body and behaves in both healthy brains and those affected by these diseases. The trial includes two groups: healthy volunteers and patients with either Alzheimer's or ALS. Individuals diagnosed with Alzheimer's or ALS and under a doctor’s care might be suitable for the patient group.

As an Early Phase 1 trial, participants will be among the first to help researchers understand how this new tracer works in humans.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that certain medications might make you ineligible if the investigator thinks they are not suitable for the study.

What prior data suggests that this brain imaging tracer is safe?

Research has shown that [11C]MPC6827, a new substance for brain imaging, has been tested in humans before. Earlier studies assessed its safety in people with advanced cancer, helping to understand how well individuals can tolerate the substance.

In those studies, [11C]MPC6827 was generally well-tolerated, with most participants experiencing no serious side effects. The substance was administered in a microdose, a very small amount, potentially enhancing safety. Participants were closely monitored to ensure their well-being.

As an early-stage study, the focus is on how the substance moves through the body and the amount of radiation absorbed. These studies are crucial for confirming the substance's safety for further research. Although detailed safety information is not yet available, this early phase indicates ongoing evaluation to confirm its safety. ^{1 2 3 4}

Why are researchers excited about this trial?

Researchers are excited about the tracer [11C]MPC6827 because it offers a novel approach to diagnosing neurodegenerative diseases. Unlike current diagnostic methods, which often rely on symptoms and less specific imaging techniques, [11C]MPC6827 is a radiotracer used in PET/CT scans to provide detailed images of the brain. This targeted imaging can potentially reveal changes in the brain associated with neurodegenerative disorders much earlier and with greater specificity. By improving early detection and understanding of these conditions, [11C]MPC6827 could pave the way for more effective treatments and interventions.

What evidence suggests that this brain imaging tracer is effective for neurodegenerative disease?

Research has shown that [11C]MPC6827 is a promising tool for imaging brain changes in diseases like Alzheimer's. This tracer targets microtubules, parts of brain cells affected by these diseases. Studies indicate that understanding microtubule problems can explain significant brain changes in these conditions. Early data from animal studies suggested that [11C]MPC6827 effectively attaches to microtubules, allowing scientists to observe crucial brain activities. This trial will involve two groups: healthy volunteers and patients with neurodegenerative disorders. The imaging could provide valuable insights into the development of neurodegenerative diseases and might aid in early diagnosis. ^{3 5 6 7}

Who Is on the Research Team?

Akiva Mintz, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for healthy volunteers and individuals with Alzheimer's or ALS. Participants must be adults, not pregnant if female, and willing to use contraception. Healthy volunteers should have no brain diseases, while those with Alzheimer's or ALS must be under a doctor's care.

Inclusion Criteria

I am not pregnant or have confirmed it with a test.

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Initial Evaluation

Five healthy volunteers receive a microdose of [11C]MPC6827 followed by whole body PET/CT to determine dosimetry and perform an initial safety evaluation

2 hours

1 visit (in-person)

Brain Imaging

Up to 30 patients with neurodegenerative disorders receive a microdose of [11C]MPC6827 and are imaged dynamically for up to 90 minutes using PET/CT

90 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including serial venous blood draws for estimation of clearance of [11C]MPC6827

48 hours

What Are the Treatments Tested in This Trial?

Interventions

• [11C]MPC6827

Trial Overview

[11C]MPC6827 is being tested in this phase 0 study to see how it spreads through the body and what dose humans can absorb safely. The first part involves five healthy volunteers; the second part compares brain imaging between normal subjects and those with neurodegenerative diseases.

How Is the Trial Designed?

Group I: Patients with Neurodegenerative Disorders Experimental Treatment 1 Intervention

Up to 30 patients with neurodegenerative disorders will receive a microdose (10 µg) of \[11C\]MPC6827 and be imaged dynamically for up to 90 minutes using PET/CT for research purposes.

Group II: Health Volunteers Experimental Treatment 1 Intervention

In the first stage, five healthy human subjects will receive a microdose (10 µg) of \[11C\]MPC6827, immediately followed by whole body PET/CT to determine dosimetry and perform an initial safety evaluation of the radiotracer. A dose of 20 mCi \[11C\]MPC6827 will be administered and serial whole body PET scans will be acquired up to 2 hours post injection.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

Several PET tracers are now clinically available for detecting amyloid-beta (Aβ) plaques in the brains of patients being evaluated for Alzheimer's disease, improving diagnostic accuracy for cognitive impairments.

Research is actively progressing on tau and α-synuclein tracers, which could enhance early diagnosis and monitoring of neurodegenerative diseases like Alzheimer's and Parkinson's, although tau tracers are still in clinical development and α-synuclein tracers are in the early research phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New protein deposition tracers in the pipeline. Jovalekic, A., Koglin, N., Mueller, A., et al.[2023]

Neurodegenerative disorders, classified as 'proteinopathies', are characterized by abnormal proteins and involve complex interactions between different proteins and neuroinflammatory cells, making accurate clinical classification challenging without biomarkers.

PET imaging is a promising tool for identifying and quantifying misfolded proteins like beta-amyloid, and ongoing research aims to develop new PET tracers for other targets such as tau and alpha-synuclein, which could enhance our understanding and diagnosis of neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Amyloid PET Imaging Biomarkers for Neurodegeneration: Focus on Tau, Alpha-Synuclein and Neuroinflammation. Catafau, AM., Bullich, S.[2019]

The PET radiotracer (d3)-[11C]MODAG-001 effectively visualizes α-synuclein aggregates in a pig model, showing high uptake in brain regions injected with α-synuclein pre-formed fibrils (α-PFF) and Alzheimer's disease homogenate, indicating its potential for early diagnosis of neurodegenerative disorders.

While (d3)-[11C]MODAG-001 demonstrated a dose-dependent effect and could be blocked by unlabeled MODAG-001, it showed limited specificity for distinguishing between different types of cerebral pathology, suggesting further development is needed for targeted applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the &#945;-synuclein PET radiotracer (d3)-[11C]MODAG-001 in pigs. Raval, NR., Madsen, CA., Shalgunov, V., et al.[2022]

The study developed two new radiolabeled ligands, N-11CH3-MPC-6827 and N-11CH3-HD-800, for PET imaging of microtubules in the brain, which could help diagnose brain diseases by penetrating the blood-brain barrier.

Both new ligands showed high specific binding in the brain and similar in vivo binding characteristics to their O-11CH3 counterparts, indicating their potential effectiveness for imaging microtubule dynamics in neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo comparison of N-11CH3 vs O-11CH3 radiolabeled microtubule targeted PET ligands. Dileep Kumar, JS., Prabhakaran, J., Damuka, N., et al.[2021]

The newly developed PET radiopharmaceutical [11C]MPC-6827 effectively quantifies destabilized neuronal microtubules in models of Alzheimer's disease, showing high selectivity and potential for clinical application.

In vivo studies demonstrated that [11C]MPC-6827 has excellent binding characteristics and metabolic stability, with over 95% stability in rat plasma and brain samples, indicating its suitability for further development in neurodegenerative disease research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding Parameters of [11C]MPC-6827, a Microtubule-Imaging PET Radiopharmaceutical in Rodents. Bansode, AH., Bhoopal, B., Gollapelli, KK., et al.[2023]

Preliminary PET imaging studies using [11C]verubulin in rodents showed varying brain uptake between mice and rats, indicating the need for further investigation into its pharmacokinetics.

In vitro studies revealed that [11C]verubulin had higher uptake in Alzheimer's Disease tissue compared to healthy controls, suggesting its potential as a biomarker for Alzheimer's pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Evaluations of [11C]Verubulin: Implications for Microtubule Imaging With PET. Lindberg, A., Mossine, AV., Aliaga, A., et al.[2021]

A new pig model was successfully established for studying α-synuclein pathology, which is crucial for developing radioligands to diagnose neurodegenerative diseases like Parkinson's Disease.

Using the amyloid-β tracer [11C]PIB, the study demonstrated significantly higher uptake in brain regions injected with α-synuclein fibrils and Alzheimer's homogenate, confirming the model's effectiveness for evaluating novel imaging agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates. Raval, NR., Nasser, A., Madsen, CA., et al.[2022]

The new PET tracer 18F-FIBT shows excellent affinity and selectivity for imaging β-amyloid deposits in the brain, making it a promising tool for diagnosing neurodegenerative diseases like Alzheimer's disease (AD).

In a small study of six patients with various cognitive impairments, 18F-FIBT demonstrated specific binding patterns consistent with AD pathology, and its uptake correlated well with clinical severity, suggesting its potential as a reliable imaging agent compared to the established tracer PiB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FIBT may expand PET for &#946;-amyloid imaging in neurodegenerative diseases. Grimmer, T., Shi, K., Diehl-Schmid, J., et al.[2022]

The review highlights the development of small molecule radiotracers for PET imaging of neurodegenerative diseases, focusing on clinically relevant radioligands targeting proteins like Aβ, tau, and α-synuclein.

It discusses the progress of these radioligands into clinical studies, while also addressing the challenges faced in developing effective imaging agents for proteinopathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tracer development for PET imaging of proteinopathies. Kallinen, A., Kassiou, M.[2022]

The preclinical studies showed that [18F]MK-6240 is safe for use, with no adverse effects observed in rats at doses up to 1000 times the anticipated clinical dose, indicating a strong safety profile for human use.

In human studies, [18F]MK-6240 demonstrated effective biodistribution for brain imaging, with a low effective dose of 5.4 mSv per scan, allowing for multiple imaging sessions per year without significant risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Koole, M., Lohith, TG., Valentine, JL., et al.[2021]

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