PET Imaging for Neuropsychiatric Disorders

Overseen By Alan Prossin, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Smoking, Pregnancy, Claustrophobia, others

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

Compensation: Varies

Number of Visits: 2

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if individuals with neuropsychiatric issues, such as mood disorders, chronic pain, dementia, or substance abuse, have increased brain inflammation. The study employs a PET scan with a radiotracer to highlight areas of inflammation. Participants may be asked to experience certain emotions or mild pain during the scan to observe brain reactions. Those diagnosed with a neuropsychiatric syndrome or who are completely healthy, right-handed, and drug-free may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if participants with neuropsychiatric syndromes need to stop their current medications. However, healthy control volunteers must be medication-free for at least 14 days before participating.

What prior data suggests that PET imaging with radiotracers [11C]PBR-28 or [11C]ER176 is safe?

Research has shown that both [11C]PBR-28 and [11C]ER176 are used in studies to image brain inflammation. These substances are injected into the bloodstream during PET scans to identify inflamed areas in the brain.

Studies have found that [11C]ER176 may provide clearer images with less variation, which is crucial for accurately assessing inflammation. Both substances have been used safely in clinical studies, with no major safety issues reported.

Since these substances are used for imaging rather than treatment, they are generally well-tolerated. However, like any medical procedure, risks exist, so discussing any concerns with the research team is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of PET imaging with radiotracers [11C]PBR-28 or [11C]ER176 for neuropsychiatric disorders because it offers a new way to visualize brain activity and inflammation, which is not possible with current treatments like medication or therapy. These radiotracers target specific proteins in the brain, providing detailed images that could help identify underlying causes of symptoms more precisely. Additionally, the incorporation of an affective challenge during PET scanning could reveal how mood and pain affect brain function, offering insights that current diagnostic methods can't provide. This unique approach could lead to more personalized treatment plans in the future.

What evidence suggests that PET imaging with radiotracers [11C]PBR-28 or [11C]ER176 is effective for identifying brain inflammation in neuropsychiatric disorders?

Research has shown that PET scans using the substances [11C]PBR-28 and [11C]ER176 can reveal brain inflammation. These substances attach to a protein related to inflammation, making it visible on the scans. In this trial, participants will undergo PET scans with either [11C]PBR-28 or [11C]ER176. Studies have found that [11C]ER176 binds more effectively, potentially making it more reliable for spotting inflammation. Imaging results have aided in understanding inflammation in mental health conditions like depression and schizophrenia. This suggests these substances could help identify inflammation linked to various brain-related conditions. ^{1 6 7 8 9}

Who Is on the Research Team?

Alan R Prossin, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults aged 18-45 who are right-handed and can sit still for long periods. It's open to healthy individuals or those with neuropsychiatric conditions like mood disorders, chronic pain, dementia, brain injuries, or substance abuse. Participants must not be pregnant, nursing, smokers, claustrophobic, drug users at the time of scanning (confirmed by a negative urine test), or have metal objects that could interfere with MRI.

Inclusion Criteria

Must be illicit drug free at time of scanning as appropriate (UDS negative)

Must be right handed

I am healthy or have a neuropsychiatric condition like mood disorder or chronic pain.

Exclusion Criteria

Must not suffer from claustrophobia

I am not pregnant or breastfeeding.

I am not a low affinity binder for PBR-28.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including PET scans and neuropsychiatric evaluations

1 week

1 visit (in-person)

PET Scanning

Participants receive PET scans with radiotracer [11C]PBR-28 or [11C]ER176 to measure microglial activation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after PET scanning

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PET with radiotracer [11C]PBR-28
• PET with radiotracer [11C]PBR-28 ( or [11C]ER176)

Trial Overview

The study aims to detect brain inflammation in people with neuropsychiatric syndromes using PET scans with radiotracers [11C]PBR-28 or [11C]ER176. Researchers want to see if there's more inflammation in patients showing stronger symptoms of these conditions.

How Is the Trial Designed?

Group I: PET with radiotracer [11C]PBR-28 or [11C]ER176 and affective challenge Experimental Treatment 2 Interventions

PET with radiotracer \[11C\]PBR-28 or \[11C\]ER176 will be performed. \[11C\]PBR-28 or \[11C\]ER176 will be injected into subjects' veins during PET scanning. Affective challenge (e.g. induction of mood, affective pain) will be presented to the patient during the PET scanning period.

Group II: PET with radiotracer [11C]PBR-28 or [11C]ER176 Experimental Treatment 1 Intervention

PET with radiotracer \[11C\]PBR-28 or \[11C\]ER176 will be performed. \[11C\]PBR-28 or \[11C\]ER176 will be injected into subjects' veins during PET scanning.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

A new radiolabeled compound, [(11)C]FEDAA1106, was successfully developed for PET imaging of the peripheral benzodiazepine receptor (PBR), which is linked to neuroinflammation and tumor progression.

The synthesis of [(11)C]FEDAA1106 achieved moderate to high chemical yields and specific activities suitable for effective imaging, indicating its potential utility in studying PBR expression in the brain and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of [11C]FEDAA1106 as a new PET imaging probe of peripheral benzodiazepine receptor expression. Wang, M., Gao, M., Hutchins, GD., et al.[2015]

The novel GluN2B-specific PET radioligand (R)-[11C]Me-NB1 was found to be safe for use in humans, with no adverse events reported during the study involving four healthy subjects.

The biodistribution results showed that the highest uptake of the radioligand occurred in the urinary bladder, spleen, and pancreas, with an effective dose coefficient of 6.0 µSv/MBq, making it suitable for repeated clinical applications in monitoring neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1. Rischka, L., Murgaš, M., Pichler, V., et al.[2023]

Functional brain imaging techniques like SPECT and PET are crucial for early diagnosis and treatment monitoring of neuropsychiatric disorders, utilizing radiopharmaceuticals that can cross the Blood Brain Barrier.

Recent advancements in radiotracer chemistry have enabled molecular imaging of neurotransmitter systems, showing promise in understanding neuropsychiatric diseases, although further studies are needed to confirm their clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiopharmaceuticals in neurological and psychiatric disorders. Valotassiou, V., Wozniak, G., Sifakis, N., et al.[2019]

Positron emission tomography (PET) is a powerful tool for studying neuropsychiatric disorders, as it can measure brain glucose metabolism and blood flow, helping to evaluate brain function in psychiatric patients.

PET technology allows researchers to assess receptor concentrations and neurotransmitter systems, providing insights into the underlying causes of conditions like schizophrenia and substance abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric disorders: investigation of schizophrenia and substance abuse. Volkow, ND., Fowler, JS.[2019]

The study evaluated (11)C-PBR28, a new tracer for imaging neuroinflammation, in a herpes simplex encephalitis model using male Wistar rats, showing it was more sensitive than the commonly used (R)-(11)C-PK11195 in detecting TSPO overexpression in various brain regions.

(11)C-PBR28 was metabolized faster than (R)-(11)C-PK11195, with a half-life of 5 minutes compared to 21 minutes, indicating its potential for quicker imaging results in preclinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195. Parente, A., Feltes, PK., Vállez García, D., et al.[2017]

This study used PET imaging with the radiotracer 11C-N-methylspiperone to compare the occupancy of serotonin (5-HT2A) and dopamine (D2) receptors in three groups: neuroleptic-free subjects, those on typical antipsychotics, and those on clozapine, revealing distinct receptor occupancy patterns among the groups.

The results showed that typical and atypical antipsychotic treatments lead to different levels of receptor occupancy, with clozapine uniquely affecting the 5-HT2A receptors, which could help in understanding the mechanisms behind the efficacy and side effects of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET measurement of neuroreceptor occupancy by typical and atypical neuroleptics. Goyer, PF., Berridge, MS., Morris, ED., et al.[2016]

Recent advancements in PET radiotracers, particularly those labeled with 18F, have enhanced the ability to study neurological diseases by allowing for the in vivo measurement of specific biological targets like receptors and proteins, which is crucial for understanding disease mechanisms.

Molecular imaging using PET and SPECT biomarkers is becoming essential for diagnosing neurological disorders, assessing treatment eligibility, and monitoring therapy progress, especially in conditions where current treatments are only supportive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative Molecular Imaging for Clinical Research, Therapeutic Stratification, and Nosography in Neuroscience. Beaurain, M., Salabert, AS., Ribeiro, MJ., et al.[2020]

Recent studies highlight the effectiveness of positron emission tomography (PET) imaging in diagnosing neuropsychiatric disorders by assessing regional neuronal activity and neuroreceptor function, particularly in conditions like schizophrenia and depression.

PET imaging also provides valuable insights into neuroinflammatory changes in the brain, which could enhance our understanding of disorders such as schizophrenia and obsessive-compulsive disorder, indicating its potential role in guiding treatment and prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on PET imaging biomarkers in the diagnosis of neuropsychiatric disorders. Hellwig, S., Domschke, K.[2020]

Recent advancements in molecular CNS imaging techniques, such as fMRI, MRS, SPECT, and PET, have significantly improved our understanding of brain function and neuropsychiatric disorders, which is crucial for developing better treatments.

Newly approved imaging agents targeting amyloid, tau, and neurotransmitter systems (like dopamine, serotonin, and opiate receptors) are now available for clinical use, enhancing the ability to diagnose and monitor CNS disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in CNS Imaging Agents: Focus on PET and SPECT Tracers in Experimental and Clinical Use. George, N., Gean, EG., Nandi, A., et al.[2018]

Recent advancements in positron emission tomography (PET) have significantly improved the ability to visualize and quantify brain processes in small animal models, achieving a spatial resolution close to 1mm, which is crucial for studying neurological disorders like Parkinson's, Alzheimer's, and Huntington's diseases.

Newly developed tracers for various neurotransmitter receptors and neuroinflammatory markers have enhanced PET's capability to investigate complex brain functions and pathologies, paving the way for better understanding and treatment of neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applications of positron emission tomography in animal models of neurological and neuropsychiatric disorders. Virdee, K., Cumming, P., Caprioli, D., et al.[2022]

A fully automated method was developed for synthesizing the radioligands [(18)F]PBR111 and [(18)F]PBR102, achieving high radiochemical yields of 30±2% and 25±2% respectively, which is efficient for clinical use.

Both tracers demonstrated excellent radiochemical purity (>99%) and high specific activity (>150GBq/μmol) within a preparation time of less than 60 minutes, making them suitable for imaging the Peripheral Benzodiazepine Receptor (PBR) in research and potentially clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of [18F]PBR111 and [18F]PBR102 using the Tracerlab FXFN and Tracerlab MXFDG module for imaging the peripheral benzodiazepine receptor with PET. Bourdier, T., Pham, TQ., Henderson, D., et al.[2015]

The study estimated the effective radiation dose of the radioligand (11)C-PBR28 in humans to be modest at 6.6 microSv/MBq, similar to other (11)C-radioligands, based on biodistribution data from 7 healthy humans and 2 rhesus monkeys.

An unusual human subject showed significantly lower uptake of (11)C-PBR28 in organs with high peripheral benzodiazepine receptor (PBR) densities, resulting in a 28% lower effective dose, indicating that individual variations in receptor binding can impact radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. Brown, AK., Fujita, M., Fujimura, Y., et al.[2022]

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11 C-ER176 displays a higher binding potential and a smaller variability of V T values. Thanks to these characteristics, clinical studies performed with 11 ...

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Specific PET Radioligand Binding to Translocator Protein

The purposes of this study are to measure the signal to noise ratio (i.e., ratio of specific to non-displaceable uptake) of 11C-(R)-PK 11195, 11C-ER176 and 11C- ...

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