Radiotracer Study for Parkinson's Disease

Recruiting at 2 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

Trial Summary

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 data supports the effectiveness of the drug 11C-M503, 11C-M503-1619, M503-1619 for Parkinson's disease?

The research highlights the importance of radiotracers in diagnosing Parkinson's disease due to their high sensitivity and specificity, which suggests that similar radiotracers like 11C-M503 could be effective in early diagnosis. However, there is no direct evidence provided about the effectiveness of 11C-M503, 11C-M503-1619, or M503-1619 specifically for treating Parkinson's disease. ^{1 2 3 4 5}

How is the drug 11C-M503 different from other Parkinson's disease treatments?

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 allows for non-invasive visualization of the disease's progression in the brain, unlike traditional treatments that focus on symptom management. ^{6 7 8 9 10}

What is the purpose of this trial?

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 11C-M503. The goal of this radiotracer is to quantify alpha-synuclein that is abnormally deposited in the brain of people with Parkinson's disease (PD). Investigators will compare uptake in participants with PD versus participants with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), as well as non-Parkinsonism volunteers. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt) (non-clinical site) Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites.

Research Team

Ilya Nasrallah, MD, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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 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]

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]

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 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]

References

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

Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

New semiquantitative assessment of 123I-FP-CIT by an anatomical standardization method. [2019]

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

Imaging of dopamine transporters in Parkinson disease: a meta-analysis of 18 F/123 I-FP-CIT studies. [2021]

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

Recent progress of imaging agents for Parkinson's disease. [2023]

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

Validation of nigrostriatal positron emission tomography measures: critical limits. [2021]

6. England pubmed.ncbi.nlm.nih.gov

The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases. [2023]

7. Germany 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. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. Austria pubmed.ncbi.nlm.nih.gov

SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT. Binding kinetics in the human brain. [2019]

10. England 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. [2019]