Radiotracer Study for Parkinson's Disease

Recruiting at 3 trial locations

Overseen By Kristi M Lelionis, MS, CCRP

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 aims to understand how the special radiotracer 11C-M503 moves through and affects the body, focusing on its ability to detect abnormal protein deposits in the brain linked to Parkinson's disease. Researchers will compare results among individuals with Parkinson's, multiple system atrophy, progressive supranuclear palsy, and healthy volunteers. The trial is ideal for those officially diagnosed with one of these conditions who are comfortable undergoing brain scans. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this novel radiotracer.

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 to get a clear answer.

What prior data suggests that this protocol is safe?

Research has shown that 11C-M503 is a new substance being tested to help create images of the brain in people with Parkinson's disease. This substance targets alpha-synuclein, a protein that accumulates in the brains of those with Parkinson's.

As this is an early phase 1 trial, the main goal is to assess the substance's safety and how the body processes it. Detailed safety information for 11C-M503 in humans is not yet available, but early trials typically aim to determine if a treatment is safe enough for further testing.

Participants in these studies might experience some side effects, but researchers closely monitor the risks. Discuss any concerns with the study team or a doctor if considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for Parkinson's disease focus on managing symptoms through medications like Levodopa, which helps replenish dopamine. However, the investigational treatment, 11C-M503, is unique because it involves a PET scan radiotracer, offering a new way to visualize and understand the brain's biology in Parkinson's patients. This treatment could potentially provide deeper insights into the disease's progression by highlighting specific brain changes. Researchers are excited about 11C-M503 because it might allow for earlier diagnosis and more personalized treatment strategies by revealing details previously inaccessible with standard imaging techniques.

What evidence suggests that this radiotracer is effective for Parkinson's disease?

Initial findings suggest that 11C-M503, which participants in this trial will receive, is a promising tool for detecting alpha-synuclein, a key protein in the brains of people with Parkinson's disease. This tool, used with PET scans, helps visualize these protein clusters in the brain. Research has shown that 11C-M503 possesses the necessary qualities for imaging studies with Parkinson's patients, potentially enhancing the identification and understanding of the disease. Although the data remains preliminary, visualizing these markers might lead to improved diagnosis and treatment strategies for Parkinson's disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Ilya Nasrallah, MD, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for people with tauopathies like Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). It also includes healthy volunteers without Parkinsonism. Participants must meet specific criteria set by the study, which are not detailed here.

Inclusion Criteria

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

Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures

Diagnosis-specific inclusion criteria: Clinical diagnoses will be determined by consensus committee for diagnostic agreement (PD, MSA, PSP or Healthy Control)

Exclusion Criteria

Contraindications or inability to tolerate imaging, arterial line or IV placement or blood draw procedures in the opinion of an investigator or treating physician

History of significant or ongoing alcohol abuse or substance abuse or dependence based on medical record review or self-reported

Females who are pregnant or breast feeding will be excluded; a urine pregnancy test will be performed in women of child-bearing potential prior to injection of 11C -M503, 11C-PiB or 18F-Florbetaben

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET Imaging

Participants undergo up to 120 minutes of dynamic brain PET scanning with 11C-M503, and may have additional imaging such as MRI and Amyloid PET scans.

1 day per session

1-2 visits (in-person)

Follow-up

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

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 11C-M503

Trial Overview The study tests a new radiotracer called 11C-M503 using brain scans like MRI and PET to see how it tracks abnormal alpha-synuclein in the brain. The goal is to compare its uptake in PD, MSA, PSP patients versus non-Parkinsonism volunteers across several research centers.

How Is the Trial Designed?

Group I: 11C-M503 PET Experimental Treatment 4 Interventions

Participants will undergo 11C-M503 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

The study presents anle253b, a diphenyl pyrazole compound, which shows high-affinity binding to α-synuclein fibrils, making it a promising candidate for imaging Parkinson's disease biomarkers.

The tracer demonstrated excellent stability in rat serum and effective penetration of the blood-brain barrier in positron emission tomography studies, indicating its potential for non-invasive detection of α-synuclein in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

11 C Radiolabeling of anle253b: a Putative PET Tracer for Parkinson's Disease That Binds to &#945;-Synuclein Fibrils in&#8197;vitro and Crosses the Blood-Brain Barrier. Maurer, A., Leonov, A., Ryazanov, S., et al.[2021]

Non-invasive nuclear radiopharmaceuticals offer a highly sensitive and specific method for the early diagnosis of Parkinson's disease, especially in atypical and preclinical cases, compared to traditional imaging techniques like CT and MRI.

Recent advancements in coordination chemistry allow for the targeted delivery of radionuclides to brain lesions by attaching them to Parkinson's disease-related transporters and receptors, enhancing the effectiveness of imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress of imaging agents for Parkinson's disease. Wu, X., Cai, H., Ge, R., et al.[2023]

In a study of 18 patients, including 11 with confirmed Parkinson's disease, there was no significant correlation between dopamine transporter (DAT) binding in the striatum and the number of surviving neurons in the substantia nigra, suggesting that DAT binding may not directly reflect neuronal survival.

The findings indicate that in Parkinson's disease, striatal DAT binding could be more related to axonal dysfunction or DAT expression rather than the actual number of healthy neurons, especially after significant neuronal damage has occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease. Saari, L., Kivinen, K., Gardberg, M., et al.[2022]

The SPECT ligand [123I]beta-CIT effectively labels dopamine transporters in the striatum and serotonin transporters in the hypothalamus-midbrain area, making it a valuable tool for studying these neurotransmitter systems in the human brain.

In patients with Parkinson's disease, there is a significant reduction in striatal activity compared to healthy individuals, indicating potential alterations in dopamine transport that could be relevant for understanding the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT. Binding kinetics in the human brain. Brücke, T., Kornhuber, J., Angelberger, P., et al.[2019]

A new semiquantitative method using Neurostat for estimating striatal uptake of 123I-FP-CIT in patients with Parkinsonian syndrome (PS) and essential tremor (ET) shows promise for more objective diagnosis, with significant differences in uptake between the two conditions.

The study found strong correlations between the new uptake measures and the severity of Parkinson's disease, indicating that these parameters can effectively aid in differentiating PS from ET and assessing disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New semiquantitative assessment of 123I-FP-CIT by an anatomical standardization method. Takada, S., Yoshimura, M., Shindo, H., et al.[2019]

In a study involving 16 macaques, striatal uptake of three PET tracers (FD, DTBZ, CFT) correlated well with striatal dopamine levels across all stages of dopamine depletion, indicating their effectiveness in measuring dopamine loss in Parkinson's disease.

However, the correlation between tracer uptake and nigral cell counts was only significant when nigral loss was less than 50%, suggesting that imaging measures may not accurately reflect disease severity in advanced stages, which could explain discrepancies between imaging results and clinical assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of nigrostriatal positron emission tomography measures: critical limits. Karimi, M., Tian, L., Brown, CA., et al.[2021]

A study involving brain samples from 9 MSA patients and 9 controls found that the radiotracer [18F]BF-227 did not show specific binding to aggregated alpha-synuclein in MSA patients, despite the presence of pathology detected by other methods.

This suggests that [18F]BF-227 may not be effective for monitoring alpha-synuclein deposition in Multiple System Atrophy, indicating a need for alternative diagnostic tools for early detection and monitoring of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid-Beta Radiotracer [18F]BF-227 Does Not Bind to Cytoplasmic Glial Inclusions of Postmortem Multiple System Atrophy Brain Tissue. Verdurand, M., Levigoureux, E., Lancelot, S., et al.[2019]

Both 18 F-FP-CIT PET and 123 I-FP-CIT SPECT imaging effectively show reduced dopamine transporter uptake in patients with Parkinson's disease (PD), indicating their potential as biomarkers for early diagnosis.

The meta-analysis included 779 PD patients and 124 healthy controls for PET studies, and 1244 PD patients and 859 controls for SPECT studies, demonstrating significant reductions in dopamine transporter uptake in key brain regions associated with PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging of dopamine transporters in Parkinson disease: a meta-analysis of 18 F/123 I-FP-CIT studies. Kong, Y., Zhang, C., Liu, K., et al.[2021]

The PET tracer [18F]ACI-12589 shows strong potential for diagnosing α-synuclein-related diseases, particularly Multiple-System Atrophy (MSA), by demonstrating clear binding in affected brain regions in a study of 23 participants.

In vivo imaging with [18F]ACI-12589 effectively distinguishes MSA patients from healthy controls and those with other neurodegenerative disorders, suggesting it could enhance diagnostic accuracy and monitor treatment responses for therapies targeting α-synuclein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases. Smith, R., Capotosti, F., Schain, M., et al.[2023]

The study analyzed brain imaging from 38 patients with parkinsonism, including 20 with Parkinson's disease (PD), using NeuroQ software to evaluate dopamine transporter and glucose metabolism, showing significant agreement with manual methods for diagnosing PD.

11C-CFT and 18F-FDG PET/CT imaging effectively distinguished PD from other conditions like multiple system atrophy (MSA) and essential tremor (ET), with specific uptake cutoffs providing accurate diagnostic criteria, particularly highlighting differences in early-stage PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Research of 11C-CFT and 18F-FDG PET in Parkinson's Disease: A Pilot Study With NeuroQ Software. Sun, X., Liu, F., Liu, Q., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40256311/

The development of a PET radiotracer for imaging alpha ... M503-1619 was identified as a promising ligand for positron emission tomography (PET) imaging of α-synuclein (α-Syn) pathology in Parkinson's disease (PD).

2. med.upenn.edu med.upenn.edu/CW2IP2/assets/user-content/documents/2023.isrs.oral.presentation.gt.asyn.m503-duplicate.pdf

The Development of [11C]M503-1619 As a PET Tracer for ... Our data suggest that [11C]M503-1619 has suitable properties for a PET radiotracer for translational imaging studies in PD subjects. Page 14. 14.

3. withpower.com withpower.com/trial/early-phase-1-tauopathies-1-2024-1ffae

Radiotracer Study for Parkinson's Disease The drug 11C-M503 is unique because it is a radiotracer used in imaging to detect alpha-synuclein fibrils, which are a key marker of Parkinson's disease. This ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12004261/

The development of a PET radiotracer for imaging alpha ... M503-1619 was identified as a promising ligand for positron emission tomography (PET) imaging of α-synuclein (α-Syn) pathology in Parkinson's disease (PD).

5. pubs.rsc.org pubs.rsc.org/en/content/articlelanding/2025/md/d5md00057b

The development of a PET Radiotracer for Imaging Alpha ... M503-1619 was identified as a promising ligand for positron emission tomography (PET) imaging of α-synuclein (α-Syn) pathology in Parkinson's disease (PD).

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06303921/

Trial | NCT06303921 11C-M503 PET EXPERIMENTAL. Participants will undergo 11C-M503 PET scan, they may also have a brain MRI and Amyloid PET scan as well as neurological assessments.