PET Imaging for Neuropsychiatric Disorders

Recruiting in Palo Alto (17 mi)

Overseen by Alan R Prossin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Smoking, Pregnancy, Claustrophobia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this research is to determine whether there is more extensive inflammation in the brain of people with clinical evidence of neuropsychiatric syndromes, such as mood disorder, chronic pain syndrome, dementia, traumatic brain injury, or substance abuse. The research will also explore whether there is more inflammation in patients with more neuropsychiatric symptoms. Inflammation in the brain will identified by using Positron Emission Tomography (PET) with the radiotracer \[11C\]PBR-28 or \[11C\]ER176.

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 data supports the effectiveness of the treatment PET with radiotracer [11C]PBR-28 for neuropsychiatric disorders?

PET imaging, including the use of radiotracers like [11C]PBR-28, has been shown to help in the early diagnosis and management of various brain disorders by providing detailed images of brain function and metabolism. This imaging technique is valuable in understanding the underlying processes of neuropsychiatric disorders and can aid in the development and monitoring of new treatments. ^{1 2 3 4 5}

Is PET imaging with [11C]PBR-28 safe for humans?

The study on [11C]PBR-28 indicates that it has been used in humans to estimate radiation doses, suggesting it is generally considered safe for human use in imaging. However, detailed safety data specific to humans is limited in the provided research. ^{6 7 8 9 10}

How does PET imaging differ from other treatments for neuropsychiatric disorders?

PET imaging is unique because it uses special tracers to create detailed images of brain activity, helping to understand the underlying causes of neuropsychiatric disorders. Unlike traditional treatments that focus on symptoms, PET imaging provides insights into brain function and neurotransmitter systems, aiding in early diagnosis and the development of new therapies. ^{1 3 4 11 12}

Research Team

Alan R Prossin, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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)

I am between 18 and 80 years old.

Must be right handed

Exclusion Criteria

I am not pregnant or breastfeeding.

Must not suffer from claustrophobia

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

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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+

Dr. LaTanya Love

The University of Texas Health Science Center, Houston

Interim President

MD from UT Medical Branch in Galveston

Dr. Jagat Narula

The University of Texas Health Science Center, Houston

Chief Academic Officer since 2023

MD, PhD

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

References

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

Radiopharmaceuticals in neurological and psychiatric disorders. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Innovative Molecular Imaging for Clinical Research, Therapeutic Stratification, and Nosography in Neuroscience. [2020]

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

Neuropsychiatric disorders: investigation of schizophrenia and substance abuse. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Update on PET imaging biomarkers in the diagnosis of neuropsychiatric disorders. [2020]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Advances in CNS Imaging Agents: Focus on PET and SPECT Tracers in Experimental and Clinical Use. [2018]

6. England 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. [2015]

7. France pubmed.ncbi.nlm.nih.gov

Synthesis of [11C]FEDAA1106 as a new PET imaging probe of peripheral benzodiazepine receptor expression. [2015]

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

Pharmacokinetic Analysis of 11C-PBR28 in the Rat Model of Herpes Encephalitis: Comparison with (R)-11C-PK11195. [2017]

9. Germany pubmed.ncbi.nlm.nih.gov

Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1. [2023]

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

Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. [2022]

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

Applications of positron emission tomography in animal models of neurological and neuropsychiatric disorders. [2022]

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

PET measurement of neuroreceptor occupancy by typical and atypical neuroleptics. [2016]