11C-HY-2-15 Radiotracer for Tauopathies

Overseen By Mary Hansbury

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Disqualifiers: Pregnancy, Schizophrenia, Alcohol abuse, others

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

Compensation: Varies

Number of Visits: 1

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new tool called 11C-HY-2-15, a radiotracer, to observe its distribution and behavior in the body and brain. The goal is to measure abnormal protein deposits in the brains of individuals with Multiple System Atrophy (MSA) and compare them to those with Parkinson's disease, progressive supranuclear palsy, and healthy individuals. Participants will undergo a special PET scan, and some may also have an MRI and other tests. This trial suits adults diagnosed with MSA, Parkinson's, or similar conditions, as well as healthy individuals interested in research participation. As an Early Phase 1 trial, this research focuses on understanding how the radiotracer functions in people, offering participants a chance to contribute to this innovative study.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that this protocol is safe?

Research shows that 11C-HY-2-15, a new imaging agent, is under study for its ability to attach to certain brain proteins linked to diseases. Animal studies found that it enters the brain and exits quickly, suggesting safety due to its short duration in the body. However, as this trial is in its early stages, limited information exists about its safety in humans. Early trials often focus on understanding how the body processes the treatment. Although initial results are promising, further research is necessary to fully understand its safety in people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the 11C-HY-2-15 radiotracer because it offers a new way to visualize tau protein deposits in the brain, which are associated with tauopathies like Alzheimer's disease. Unlike current treatments that primarily focus on alleviating symptoms or slowing progression, 11C-HY-2-15 provides a diagnostic edge by enabling more precise imaging of tau protein aggregates. This could lead to earlier and more accurate diagnosis, helping tailor treatment strategies to individual patients and potentially improving outcomes.

What evidence suggests that this radiotracer is effective for quantifying alpha-synuclein in tauopathies?

Studies have shown that the radiotracer 11C-HY-2-15, which participants in this trial will receive, effectively attaches to alpha-synuclein, a protein that clumps in the brains of people with conditions like Multiple System Atrophy (MSA). This radiotracer helps create images of these protein clumps using a PET scan, allowing doctors to see the location and amount of the protein in the brain. Research indicates that 11C-HY-2-15 concentrates more in certain brain areas, like the pallidum and midbrain, in patients with conditions such as Progressive Supranuclear Palsy (PSP). This suggests it might provide clear images of these protein deposits, aiding in better diagnosis and understanding of these diseases. Although studies in humans are still in the early stages, initial results are promising for its use in imaging alpha-synuclein in the brain. ^{2 4 6 7 8}

Who Is on the Research Team?

Ilya Nasrallah, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults aged 40-80 with Multiple System Atrophy (MSA), Parkinson's disease (PD), progressive supranuclear palsy (PSP), or healthy volunteers can join. Participants must understand the study and consent, or have a partner to assist. Brain donation is optional for PD/MSA/PSP subjects.

Inclusion Criteria

Participants must be informed of the investigational nature of this study and be willing to provide written informed consent

Participants must be willing to participate in this study in accordance with institutional and federal guidelines

Participants who are deemed unable to provide informed consent must have a designated study partner present for consent and to accompany them to study visits

Exclusion Criteria

Contraindication to MRI, such as non-compatible implanted medical device

You have a serious mental illness like schizophrenia or bipolar disorder. Having major depression is okay.

You have a history of serious alcohol or drug problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET Imaging

Participants undergo 11C-HY-2-15 PET scan to determine biodistribution, metabolism, excretion, and brain uptake. May include brain MRI and neurological assessments.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after PET imaging, including collection of adverse events.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 11C-HY-2-15

Trial Overview

The trial tests a new brain imaging agent called 11C-HY-2-15 in MSA patients compared to those with PD, PSP, and healthy individuals. It involves neurological assessments, PET scans for amyloid and alpha-synuclein proteins, and MRI of the brain.

How Is the Trial Designed?

Group I: 11C-HY-2-15 PET Experimental Treatment 4 Interventions

Participants will undergo 11C-HY-2-15 PET scan, they may also have a brain MRI and Amyloid PET scan as well as neurological assessments

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

New imaging agents for tau fibrils have been developed to improve the diagnosis of Alzheimer's disease and other tauopathies, showing high contrast in PET studies with human subjects.

Second-generation tau PET probes have been created to specifically target tau pathologies, with one novel radiocompound demonstrating the ability to differentiate between AD and non-AD tau aggregates, enhancing diagnostic evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET Imaging. Higuchi, M.[2020]

The novel PET tracer 18F-RO-948 shows superior binding characteristics for detecting tau pathology in Alzheimer's disease compared to other tracers 11C-RO-963 and 11C-RO-643, based on human evaluations involving amyloid PET-positive AD subjects and healthy controls.

In the study, 18F-RO-948 effectively discriminated between Alzheimer's patients and healthy individuals, revealing significant differences in tau accumulation across multiple brain regions, indicating its potential as a valuable tool for diagnosing and understanding Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of 3 Novel Tau Radiopharmaceuticals, 11C-RO-963, 11C-RO-643, and 18F-RO-948, in Healthy Controls and in Alzheimer Subjects. Wong, DF., Comley, RA., Kuwabara, H., et al.[2019]

The novel compound [18F] JNJ-64326067 shows promise for detecting tau aggregates in the brain, with significant retention observed in 4 out of 5 participants with probable Alzheimer's disease, indicating its potential efficacy in identifying neurodegenerative changes.

The dosimetry results suggest that [18F] JNJ-64326067 has a low effective dose for both males and females, making it a safe option for imaging tau pathology in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer's disease. Schmidt, ME., Janssens, L., Moechars, D., et al.[2021]

The novel tau-PET radiotracer [18F]PI-2620 shows strong potential as a surrogate biomarker for neuronal injury, correlating well with traditional [18F]FDG-PET imaging in a study of 26 subjects with suspected tauopathies.

Early-phase imaging of [18F]PI-2620 (0.5 to 2.5 minutes post-injection) demonstrated high agreement with [18F]FDG-PET, suggesting that it could replace the need for additional [18F]FDG-PET imaging in assessing both tau distribution and neuronal injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury. Beyer, L., Nitschmann, A., Barthel, H., et al.[2022]

Dynamic PET imaging with the tau radiotracer [18F]PI-2620 effectively distinguishes patients with progressive supranuclear palsy (PSP) from healthy controls, with a high accuracy demonstrated by area under the curve (AUC) values around 0.96.

Truncated acquisition times of 0-40 minutes provide a good balance of accuracy and efficiency for tau-PET imaging, maintaining similar discrimination capabilities as the full 60-minute scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of short imaging protocols for [18F]PI-2620 tau-PET in progressive supranuclear palsy. Song, M., Scheifele, M., Barthel, H., et al.[2022]

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Nonhuman primate PET studies confirmed that [11C]HY-2-15 achieved moderate brain uptake (SUV ~1.6) and rapid washout [157]. These properties position [11C]HY-2- ...

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Here, we demonstrate that [3H]HY-2-15 has the capability to bind to aggregated alpha-synuclein in multiple system atrophy brain and tau aggregations in ...

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Development of Positron Emission Tomography Radiotracers ...

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