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

17 Participants Needed

Trial Summary

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 evidence supports the effectiveness of the drug [11C]Verubulin for neurodegenerative diseases?

Preliminary studies show that [11C]Verubulin, a drug used for brain imaging, has higher uptake in Alzheimer's disease tissue compared to healthy tissue, suggesting it may help in identifying disease-related changes. ^{1 2 3 4 5}

Is [11C]MPC6827 safe for use in humans?

[11C]MPC6827 has shown high stability in rat plasma and brain samples, indicating it is generally stable in the body. However, more studies are needed to fully understand its safety in humans. ^{2 6 7 8 9}

How does the drug [11C]Verubulin differ from other treatments for neurodegenerative diseases?

[11C]Verubulin is unique because it is a PET imaging tracer specifically designed to visualize microtubules in the brain, which can help in understanding neurodegenerative diseases like Alzheimer's. Unlike other treatments that target symptoms or protein aggregates, this drug aids in diagnosing and studying the disease's progression by providing detailed brain images. ^{2 3 5 7 10}

What is the purpose of this trial?

This is a phase 0 study that will enable an assessment of biodistribution and estimation of absorbed dose in humans based on data collected from five healthy volunteers, which is typically the minimum number required by the FDA for first-in-human studies to assess dosimetry of a new tracer. The evaluation of the brain imaging of thirty additional subjects in the 2nd part of the study will lead to a descriptive assessment of the targeting and pharmacokinetics of MPC6827 in the brain and between normal and diseased brain.

Research Team

Akiva Mintz, MD

Principal Investigator

Columbia University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

New protein deposition tracers in the pipeline. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Preliminary Evaluations of [11C]Verubulin: Implications for Microtubule Imaging With PET. [2021]

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

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

4. England pubmed.ncbi.nlm.nih.gov

18F-FIBT may expand PET for &#946;-amyloid imaging in neurodegenerative diseases. [2022]

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

Tracer development for PET imaging of proteinopathies. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Binding Parameters of [11C]MPC-6827, a Microtubule-Imaging PET Radiopharmaceutical in Rodents. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

An in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates. [2022]

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

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. [2021]

9. England pubmed.ncbi.nlm.nih.gov

In vivo comparison of N-11CH3 vs O-11CH3 radiolabeled microtubule targeted PET ligands. [2021]

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

Evaluation of the &#945;-synuclein PET radiotracer (d3)-[11C]MODAG-001 in pigs. [2022]