Neuroinflammation Imaging for Alzheimer's Disease

Overseen By IIya Nasrallah, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Disqualifiers: Epilepsy, Head trauma, Nicotine dependence, others

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

Compensation: Varies

Number of Visits: 3

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to better understand brain inflammation in individuals with Alzheimer's Disease or Mild Cognitive Impairment through advanced imaging techniques. Participants will undergo a PET/CT scan with a special tracer ([11C]PBR28 or [18F]NOS) to visualize brain activity. Those with a specific genetic trait may join a sub-study involving an additional scan for comparison. This trial suits individuals with Alzheimer's, Mild Cognitive Impairment, or those who are healthy and part of a specific research group. Participants should not have a history of seizures or tobacco use, among other criteria. As an Early Phase 1 trial, this research focuses on understanding how the imaging techniques function in people, offering participants a unique opportunity to contribute to groundbreaking scientific knowledge.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

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 understand any specific requirements.

What prior data suggests that this imaging technique is safe for humans?

Research has shown that the investigational tracer [11C]PBR28 has been studied in people with Alzheimer's disease. It binds to certain proteins associated with brain inflammation. Studies have not reported major safety concerns for [11C]PBR28, but results can vary among individuals.

In contrast, [18F]NOS has mostly been tested in animals like mice, and limited information exists on its safety in humans. This study is in an early phase, so researchers are still learning how people handle [18F]NOS. This phase focuses on understanding side effects and how the body processes the tracer.

Joining a clinical trial is a significant decision. Discuss any concerns with the study team and ask questions about the safety of these tracers. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial because it explores innovative imaging techniques to better understand neuroinflammation in Alzheimer's disease. Unlike standard treatments that often focus on symptom management, this trial uses [11C]PBR28 and [18F]NOS to visualize neuroinflammation, potentially revealing new insights into disease progression and treatment effects. These imaging agents can detect subtle changes in the brain, offering a clearer picture of inflammation's role in Alzheimer's, which could lead to more targeted therapies in the future.

What evidence suggests that this imaging technique is effective for studying neuroinflammation in Alzheimer's Disease?

In this trial, [11C]PBR28 is one of the substances under study. Research has shown that [11C]PBR28 can effectively detect brain inflammation in people with Alzheimer's. This substance absorbs more in brain areas affected by Alzheimer's than in healthy individuals, suggesting it could help identify brain inflammation.

Another substance under study is [18F]NOS. Most information about [18F]NOS comes from animal studies, but it targets specific inflammation markers in the brain. This method aims to visualize inflammation using PET/CT scans. Early studies indicate it might be a useful tool for understanding inflammation related to Alzheimer's. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for men and women over 55, either healthy or with Alzheimer's/Mild Cognitive Impairment. Healthy participants need a negative amyloid PET scan and an MMSE score of 28+. Those with Alzheimer's should have a positive amyloid PET scan and an MMSE score of 14-27. All must be part of the UPenn ADC cohort, informed about the study's nature, consent in writing, and follow guidelines.

Inclusion Criteria

I am 55 years old or older.

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.

A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be positive by the study PI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Imaging and Blood Sampling

Participants undergo PET/CT scans using [18F]NOS and possibly [11C]PBR28, along with blood sampling

1 day

1-2 visits (in-person)

MRI Scan

Participants must have an MRI scan if a recent one is not available

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [11C]PBR28
• [18F]NOS

Trial Overview

The study tests two brain imaging agents ([18F]NOS and [11C]PBR28) using PET/CT scans to understand brain inflammation in Alzheimer’s Disease/Mild Cognitive Impairment versus healthy subjects. Some may also join a sub-study comparing both tracers. Participants will undergo blood tests and possibly an MRI.

How Is the Trial Designed?

Group I: AD/MCI or HC with Genetic Polymorphism Experimental Treatment 1 Intervention

Sub-Study: Subjects have a specific genetic polymorphism andare diagnosed with Alzheimer's Disease (AD)/Mild Cognitive Imparment (MCI) or are healthy volunteers/controls (HC).

Group II: AD/MCI or HC Experimental Treatment 1 Intervention

Main Study: Subjects are diagnosed with Alzheimer's Disease (AD)/Mild Cognitive Imparment (MCI) or are healthy volunteers/controls (HC).

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Neuroinflammation is a key factor in the development of Alzheimer's disease, with increased glial cell activation observed in both animal models and human patients, highlighting its potential role in disease progression.

Current imaging techniques, such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS), are being explored to non-invasively detect and quantify neuroinflammation, which could improve early diagnosis and therapeutic monitoring in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo molecular imaging of neuroinflammation in Alzheimer's disease. Chaney, A., Williams, SR., Boutin, H.[2020]

The compound [(18)F]9 was identified as a promising PET tracer for imaging inducible nitric oxide synthase (iNOS), showing higher uptake in the lungs of mice with LPS-induced iNOS activation compared to control mice.

In vivo studies confirmed the specificity of [(18)F]9 for iNOS, as tracer uptake was significantly reduced when a known iNOS inhibitor was used, indicating its potential for accurate imaging of iNOS activation in inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase. Zhou, D., Lee, H., Rothfuss, JM., et al.[2021]

In a pilot study involving 10 adults (6 with Parkinson's disease and 4 healthy controls), researchers found that neuroinflammation, indicated by increased levels of the [18F]NOS radiotracer, was significantly higher in Parkinson's patients compared to healthy individuals.

The study suggests that [18F]NOS PET imaging could be a valuable non-invasive tool for measuring neuroinflammation in early-stage Parkinson's disease, highlighting the role of oxidative stress in the disease's pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease. Doot, RK., Young, AJ., Nasrallah, IM., et al.[2023]

PET and SPECT imaging techniques are crucial for the early diagnosis and study of Alzheimer's disease (AD) by allowing for the in vivo measurement of key biomarkers associated with the disease.

Several promising radioligands, such as [11C]MP4A and [18F]FDDNP, have shown high selectivity and specificity for binding sites in AD patients, indicating their potential for effective diagnostic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Alzheimer's disease imaging agents for clinical studies. Ryu, EK., Chen, X.[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]

The study successfully developed a new PET imaging tracer, [18F]FBAT, which can detect inducible nitric oxide synthase (iNOS) activity in a mouse model of neuroinflammation, indicating its potential as a biomarker for neuroinflammation.

In vivo imaging showed that [18F]FBAT accumulation was significantly higher in LPS-treated mice compared to controls, and this accumulation was reduced by an iNOS inhibitor, confirming the tracer's specificity for iNOS in neuroinflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated Synthesis and Initial Evaluation of (4'-Amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-[18F]fluorophenyl)methanone for PET/MR Imaging of Inducible Nitric Oxide Synthase. Yeh, SH., Huang, WS., Chiu, CH., et al.[2021]

The study demonstrated that 18F-PBR-111 PET imaging can effectively identify neuroinflammation in specific brain regions of cuprizone-treated mice, indicating its potential as a marker for multiple sclerosis (MS) research.

Significant uptake of 18F-PBR-111 was observed in areas associated with neuroinflammation, such as the corpus callosum and striatum, and this uptake correlated with the presence of activated microglia, suggesting its utility for evaluating treatment responses in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of 18F-PBR-111 in the Cuprizone Mouse Model of Multiple Sclerosis. Jewells, VL., Yuan, H., Merrill, JR., et al.[2021]

The study demonstrated that myocardial (18)F-NOS activity is significantly higher in heart transplant patients experiencing organ rejection, indicating its potential as a marker for assessing iNOS activity related to inflammation.

The (18)F-NOS radiopharmaceutical showed acceptable radiation exposure levels, with the bladder wall being the critical organ, suggesting it could be safely used in humans for monitoring iNOS levels in various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans. Herrero, P., Laforest, R., Shoghi, K., et al.[2021]

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