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[18F]Mc225

This article discusses clinical trials investigating [18F]MC225, a radiotracer used in PET imaging to measure P-glycoprotein (P-gp) function in the brain. Current trials are evaluating [18F]MC225 in patients with treatment-resistant depression and neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, and mild cognitive impairment. These Phase 2 studies aim to assess how P-gp activity differs in these conditions.

Table of Contents

Overview of [18F]MC225 Clinical Research

[18F]MC225 is a radiotracer being investigated in clinical trials for its ability to measure P-glycoprotein (P-gp) function in the brain using PET/CT imaging. Currently, two Phase 2 clinical trials have been authorized to study this imaging agent in different patient populations[1][2].

The chemical name of [18F]MC225 is 5-(1-(2-[18F]fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen. This compound is labeled with fluorine-18, a radioactive isotope that allows it to be detected by PET scanners[2].

These clinical trials represent important research efforts to understand how P-glycoprotein activity may be altered in various brain disorders. The trials are investigating both psychiatric conditions, specifically treatment-resistant depression, and neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and mild cognitive impairment[1][2].

Understanding P-glycoprotein Function

P-glycoprotein is a protein that functions as a transporter in cell membranes throughout the body, with particularly important roles at the blood-brain barrier. This barrier is a protective system that controls which substances can enter brain tissue from the bloodstream.

P-gp acts as an efflux pump, meaning it actively pumps certain substances out of cells and prevents them from entering the brain. This mechanism serves several important functions:

  • Protection: P-gp helps protect the brain from potentially toxic compounds by preventing their entry into brain tissue
  • Drug transport: P-gp can affect how medications reach the brain, which may influence treatment effectiveness
  • Disease involvement: Changes in P-gp function have been linked to various neurological and psychiatric conditions

Understanding P-gp activity in different disease states may help explain why some patients respond to treatments while others do not, and could lead to better therapeutic approaches.

Clinical Trial in Treatment-Resistant Depression

The first authorized trial (2023-508303-20-01) is investigating the role of P-glycoprotein in treatment-resistant depression (TRD). This Phase 2 interventional study plans to enroll 44 participants[1].

The primary aim of this study is to assess the involvement of P-gp in TRD by comparing P-gp activity between two groups of patients:

  • Subjects with treatment-resistant depression: Patients whose depression has not responded adequately to standard antidepressant treatments
  • Subjects with treatment-responsive depression (DRESP): Patients whose depression has responded well to antidepressant medications

The study uses [18F]MC225 PET/CT imaging to measure P-gp activity in the brain. The hypothesis behind this research is that differences in P-gp function may explain why some patients respond to antidepressant medications while others do not[1].

If P-gp is more active in patients with treatment-resistant depression, it might be pumping antidepressant medications out of the brain before they can have their therapeutic effect. This would represent an important mechanism of treatment resistance and could point to new therapeutic strategies.

Clinical Trial in Neurodegenerative Diseases

The second authorized trial (2024-518865-85-00) is evaluating [18F]MC225 to measure P-glycoprotein function in patients with neurodegenerative diseases. This Phase 2 study plans to enroll 30 participants[2].

The trial is investigating three related neurodegenerative conditions:

  • Alzheimer’s disease: A progressive brain disorder that causes memory loss and cognitive decline, characterized by the buildup of abnormal proteins in the brain
  • Mild Cognitive Impairment (MCI): A condition involving noticeable decline in cognitive abilities that is greater than expected for age but not severe enough to interfere significantly with daily activities; MCI may progress to Alzheimer’s disease
  • Parkinson’s disease: A progressive disorder affecting movement and coordination, caused by loss of nerve cells in specific brain regions

Changes in P-glycoprotein function have been observed in neurodegenerative diseases and may contribute to disease progression. P-gp alterations could affect the accumulation of toxic proteins in the brain or influence how medications used to treat these conditions reach their targets[2].

This trial aims to characterize P-gp function across these different neurodegenerative conditions, which may help researchers understand disease mechanisms and develop better treatments.

How [18F]MC225 is Administered

[18F]MC225 is administered as an intravenous injection, meaning it is injected directly into a vein. The dose used in the clinical trial for neurodegenerative diseases is 400 MBq (megabecquerel), which is a unit measuring radioactivity[2].

The administration process typically involves the following steps:

  • Preparation: The radiotracer is prepared in a specialized facility and must be used within a short time frame due to the radioactive decay of fluorine-18
  • Injection: The [18F]MC225 solution is injected intravenously, usually into an arm vein
  • Distribution: After injection, the radiotracer circulates through the bloodstream and crosses into the brain
  • Imaging: PET/CT scanning is performed to detect where the radiotracer accumulates in the brain

The amount of radiation exposure from [18F]MC225 is comparable to other diagnostic nuclear medicine procedures and is considered safe for research purposes when appropriate safety protocols are followed.

What the Trials are Measuring

Both clinical trials use specialized imaging measurements to assess P-glycoprotein function in the brain. These measurements provide quantitative data about how [18F]MC225 is distributed in brain tissue.

The trial in treatment-resistant depression is measuring P-gp activity by assessing [18F]MC225 standardized uptake value (SUV) and volume distribution (VD) in the whole brain. SUV is a measurement that indicates how much radiotracer has accumulated in brain tissue, while volume distribution describes how the tracer spreads throughout the brain[1].

The trial in neurodegenerative diseases is measuring regional PET tracer uptake and influx values of [18F]MC225. This approach examines specific brain regions rather than the whole brain, which may reveal regional differences in P-gp function that are relevant to different neurodegenerative diseases[2].

Key measurements being assessed include:

  • Uptake values: How much [18F]MC225 accumulates in different brain regions, which reflects P-gp activity (higher uptake may indicate lower P-gp activity, as less tracer is being pumped out)
  • Influx values: The rate at which [18F]MC225 enters brain tissue from the bloodstream
  • Regional patterns: Differences in tracer distribution across various brain areas, which may correlate with disease-specific patterns
  • Comparison between groups: Differences in measurements between patients with different conditions or treatment responses

These measurements will help researchers understand whether P-glycoprotein function is altered in treatment-resistant depression and neurodegenerative diseases, and whether these alterations follow specific patterns that could be clinically meaningful.

The data collected from these Phase 2 trials will be important for determining whether [18F]MC225 PET imaging can serve as a useful tool for understanding disease mechanisms, predicting treatment responses, or monitoring disease progression in these conditions.

Trial ID Phase Conditions Studied Status Enrollment Primary Outcome
2023-508303-20-01 Phase 2 Treatment-resistant depression Authorised 44 P-gp activity measured by [18F]MC225 SUV and VD in whole brain
2024-518865-85-00 Phase 2 Parkinson’s disease, Alzheimer’s disease, Mild Cognitive Impairment Authorised 30 Regional PET tracer uptake and influx values of [18F]MC225

FAQ

  • What is [18F]MC225 and what are clinical trials studying it for? [18F]MC225 is a radiotracer used in PET/CT imaging to measure P-glycoprotein (P-gp) function in the brain. Clinical trials are studying it to evaluate P-gp activity in treatment-resistant depression and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and mild cognitive impairment.
  • What conditions are being studied in [18F]MC225 clinical trials? Current trials are investigating [18F]MC225 in two main areas: treatment-resistant depression (comparing patients who respond to treatment versus those who don't) and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and mild cognitive impairment.
  • What phase are the [18F]MC225 clinical trials in? The current clinical trials investigating [18F]MC225 are in Phase 2. This phase typically evaluates the effectiveness of the imaging agent and optimal dosing in specific patient populations.
  • How many patients are participating in [18F]MC225 trials? One trial is enrolling 44 participants with treatment-resistant and treatment-responsive depression, while another trial is enrolling 30 participants with neurodegenerative diseases. Both trials use PET/CT imaging with [18F]MC225 to measure P-glycoprotein function.
  • How is [18F]MC225 administered in these clinical trials? [18F]MC225 is administered intravenously at a dose of 400 MBq (megabecquerel). After administration, PET/CT imaging is performed to measure the uptake and distribution of the radiotracer in the brain, which reflects P-glycoprotein activity.

Ongoing Clinical Trials on [18F]Mc225

  • Study on Brain Activity in Treatment-Resistant Depression Using [18F]MC225 for Patients with Depression

    Recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Italy

  • Study of [18F]MC225 to Assess P-glycoprotein Function in Patients with Alzheimer’s, Mild Cognitive Impairment, and Parkinson’s Disease

    Not yet recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    The Netherlands

Glossary

  • P-glycoprotein (P-gp): A protein found in cell membranes, particularly in the blood-brain barrier, that acts as a pump to remove certain substances from cells. It plays a role in protecting the brain from potentially harmful compounds and can affect how medications reach brain tissue.
  • PET/CT imaging: Positron Emission Tomography combined with Computed Tomography. A medical imaging technique that uses a radioactive tracer to create detailed pictures of organs and tissues inside the body, showing both structure and function.
  • Radiotracer: A radioactive substance used in medical imaging that is injected into the body to help visualize specific organs, tissues, or biological processes. The radiation it emits is detected by imaging equipment to create pictures.
  • Treatment-resistant depression (TRD): A form of depression that does not respond adequately to at least two different antidepressant treatments given at appropriate doses and duration. Patients continue to experience significant depressive symptoms despite treatment.
  • Standardized uptake value (SUV): A measurement used in PET imaging that indicates how much radiotracer has accumulated in a specific area of the body. It helps quantify the level of activity or function in that region.
  • Volume distribution (VD): A measure of how a substance, such as a radiotracer, spreads throughout a tissue or organ. In brain imaging, it indicates how the tracer is distributed across different brain regions.
  • Mild Cognitive Impairment (MCI): A condition involving noticeable decline in cognitive abilities, including memory and thinking skills, that is greater than expected for a person's age but not severe enough to interfere significantly with daily life. It may be an early stage of Alzheimer's disease.
  • Megabecquerel (MBq): A unit of measurement for radioactivity. One megabecquerel equals one million radioactive disintegrations per second. It is used to measure the dose of radioactive tracers given in medical imaging.
  • Blood-brain barrier: A protective barrier formed by specialized cells that line blood vessels in the brain. It controls which substances can pass from the bloodstream into brain tissue, protecting the brain from harmful compounds while allowing essential nutrients through.
  • Neurodegenerative disease: A group of disorders characterized by progressive loss of nerve cells in the brain, leading to declining mental and/or physical function. Examples include Alzheimer's disease and Parkinson's disease.

References

  1. https://clinicaltrials.gov/study/2023-508303-20-01
  2. https://clinicaltrials.gov/study/2024-518865-85-00