Radialis PET Imager for Alzheimer's Disease

(Amyloid RPI Trial)

Overseen By Ur Metser

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Pregnancy, Inability to consent, others

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

Compensation: Varies

Number of Visits: 2

160 Participants Needed

Trial Summary

What is the purpose of this trial?

The standard or usual workup for cognitive impairment, including Alzheimer's Disease, may include brain amyloid PET with PET/CT or PET/MR imaging. Amyloid PET is the standard imaging that was requested for you by your referring physician. This imaging can visualize your brain. With the development of new therapies for Alzheimer's disease which require amyloid PET imaging, there will be a significant increase in the number of PET scans needed to provide care to all patients. There are likely not enough PET scanners in Canada to meet this demand. Therefore, we are searching for comparable alternatives. One of the imaging devices that was introduced in the clinic is the Radialis PET imager (or RPI). Health Canada, the regulatory body that oversees the use of devices in Canada, has not approved the sale or use of the Radialis PET imager. Health Canada has allowed the Radialis PET imager to be used in this study. We would like to see whether the images obtained for the brain are comparable to those obtained from a PET/CT or PET/MRI scanner. It is a new type of PET imaging device for patients undergoing a PET scan and has been used in Canada for research. RPI is experimental, meaning that this PET scan is not used routinely in patients' care. In comparison to the standard PET devices, RPI is smaller and mobile, meaning it can be moved around easily for use. Also, it can be installed in imaging centers at a lower cost. These advantages make RPI an interesting alternative to the standard PET. However, the performance of this new imaging device has not been tested in Amyloid PET imaging in particular. As you may know, in a PET scan, we inject a radioactive material (called tracer) which can circulate in your body and visualize specific areas in your body. In amyloid PET we inject an amyloid tracer that goes to the brain and lights up certain regions of the brain. RPI was previously tested for other PET tracers and was shown to be comparable to standard PET devices. Thus, by changing the PET material (to Amyloid), we are pursuing the same aim: comparison of RPI with standard PET devices and see whether it can provide comparable images of the brain.

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 is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the Radialis PET Imager treatment for Alzheimer's Disease?

Research shows that PET imaging, like the Radialis PET Imager, can help detect changes in brain metabolism and structure associated with Alzheimer's Disease. This can improve the accuracy of diagnosing and predicting the progression of the disease, which is crucial for effective treatment planning. ^{1 2 3 4 5}

How does the Radialis PET Imager treatment for Alzheimer's disease differ from other treatments?

The Radialis PET Imager is unique because it focuses on advanced imaging techniques to improve the diagnosis and understanding of Alzheimer's disease, rather than directly treating the symptoms. This approach uses PET imaging to provide detailed insights into brain changes, which can help in early detection and monitoring of the disease, setting it apart from traditional drug treatments that aim to manage symptoms. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for individuals with cognitive impairment or Alzheimer's disease who need amyloid PET imaging. Participants must be eligible for standard brain amyloid PET scans as part of their usual care. The Radialis PET imager hasn't been approved by Health Canada but can be used in this study.

Inclusion Criteria

I can stay still for an extra 30-45 minutes for a scan.

Patients with cognitive impairment undergoing the standard of care brain 18F-Florbetaben PET imaging

Exclusion Criteria

I am unable to understand or sign the consent form.

I cannot have a PET scan due to pregnancy or difficulty staying still.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I - Optimization

Optimization of brain PET imaging technique and data reconstruction methods using RPI. Up to 10 patients will be recruited and scanned on the RPI camera after their clinical PET scan.

3 months

1 visit (in-person) per patient

Phase II - Validation

Validation of RPI against standard PET for amyloid PET imaging. 150 patients will be assessed using the finalized imaging protocol.

18 months

1 visit (in-person) per patient

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures.

4 weeks

Treatment Details

Interventions

• Radialis PET Imager

Trial Overview The trial is testing the Radialis PET Imager (RPI), a new, mobile and potentially more affordable alternative to standard PET/CT or PET/MR scanners, to see if it provides comparable brain images when using an amyloid tracer.

Participant Groups

Group I: Single arm, observational Experimental Treatment 1 Intervention

Single arm, observational

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

MRI and PET brain imaging have greatly enhanced the understanding and diagnosis of various dementia syndromes over the past 20 years, helping to identify specific patterns and effects on brain function.

These imaging techniques are now commonly used in clinical trials to determine eligibility and measure treatment outcomes, highlighting their importance in advancing dementia research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain imaging in dementia. Bonifacio, G., Zamboni, G.[2017]

New diagnostic criteria for Alzheimer's disease (AD) focus on biomarkers related to synaptic dysfunction and neurodegeneration, enhancing clinical detection methods.

Advanced imaging techniques like MRI and PET scans can effectively identify key indicators of AD, such as medial-temporal atrophy and amyloid protein retention, aiding in diagnosis and monitoring treatment progress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brain imaging of Alzheimer' disease: state of the art and perspectives for clinicians]. Trombella, S., Assal, F., Zekry, D., et al.[2016]

In a study of 167 patients with mild cognitive problems, PET scans measuring brain metabolism were able to predict cognitive decline, showing that 94% of patients with positive scans progressed in their condition compared to only 25% with negative scans.

The results suggest that using PET scans can significantly enhance the accuracy of predicting the clinical course of cognitive decline, with a relative risk of 3.8 for those predicted to decline and 18.4 for those expected to remain stable but who had positive scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of regional cerebral metabolism in patients undergoing dementia evaluation: comparison to a quantifying parameter of subsequent cognitive performance and to prognostic assessment without PET. Silverman, DH., Truong, CT., Kim, SK., et al.[2016]

SPECT scanning can effectively differentiate between early Alzheimer's disease (AD) and healthy elderly individuals by measuring regional cerebral blood flow (rCBF), particularly in the prefrontal and parietal cortices.

In a study of 28 subjects (18 with early AD and 10 healthy controls), significant reductions in rCBF were observed in specific brain regions of AD patients, suggesting that SPECT could be a valuable diagnostic tool when standardized techniques are applied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional cerebral blood flow deficits in mild Alzheimer's disease using high resolution single photon emission computerized tomography. Trollor, JN., Sachdev, PS., Haindl, W., et al.[2016]

A novel multimodal imaging marker, developed using a deep learning algorithm, can predict which patients with mild cognitive impairment (MCI) are most likely to decline to dementia, enhancing the efficiency of clinical trials.

Using this imaging marker as an inclusion criterion can reduce the required sample size for trials by at least five times, allowing for smaller, more statistically powerful studies compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging-based enrichment criteria using deep learning algorithms for efficient clinical trials in mild cognitive impairment. Ithapu, VK., Singh, V., Okonkwo, OC., et al.[2018]

The automated cortical surface mapping (CSM) method for analyzing PET scans significantly improves the efficiency of extracting regional data, making it easier to classify Alzheimer's disease patients compared to those with mild cognitive impairment and healthy controls.

Using a single set of VOIs generated through this automated process resulted in better classification accuracy than traditional manual methods, indicating that it can reduce measurement variance and enhance the reliability of PET data analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated VOI Analysis in FDDNP PET Using Structural Warping: Validation through Classification of Alzheimer's Disease Patients. Wilks, MQ., Protas, H., Wardak, M., et al.[2021]

High-resolution SPECT imaging can help diagnose Alzheimer's disease (AD) by identifying specific patterns of reduced blood flow in the brain, particularly in the frontal and temporoparietal areas, which are often affected early in the disease.

In patients with mild cognitive symptoms, SPECT can enhance diagnostic accuracy by revealing focal hypoperfusion, while in those with probable AD, it can confirm the diagnosis when combined with findings of brain atrophy from CT scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional brain imaging with single-photon emission computed tomography in the diagnosis of Alzheimer's disease. Waldemar, G., Høgh, P., Paulson, OB.[2019]

The study developed a standardized voxel of interest (VOI) template that significantly improves the ability to distinguish between Alzheimer's disease (AD) patients and healthy controls using the PET radioligand 11C-PIB, achieving complete separation in a test cohort of 9 AD and 4 control subjects.

This VOI template, which can potentially replace manual delineation methods, offers a more efficient and automated approach for assessing amyloid-beta accumulation in clinical settings, enhancing diagnostic capabilities for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease. Mikhno, A., Devanand, D., Pelton, G., et al.[2021]

The ROVER software provides a new way to analyze brain (18)F-FDG-PET images, showing that it can accurately measure brain glucose uptake and distinguish between Alzheimer's disease (AD) patients and healthy controls in a pilot study of 14 AD patients and 18 controls.

ROVER-derived brain volumes were significantly lower in AD patients compared to controls, with diagnostic accuracy comparable to traditional voxel-based analyses, indicating its potential as a valuable tool for assessing brain metabolism in AD and other neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of estimation of brain volume and 2-deoxy-2-(18)F-fluoro-D-glucose metabolism using a novel automated image analysis method: application in Alzheimer's disease. Musiek, ES., Saboury, B., Mishra, S., et al.[2016]

A new semiautomated method for defining regions of interest (ROIs) in SPECT imaging was tested on 10 patients with probable Alzheimer's disease and 7 healthy subjects, showing promise for more accurate diagnosis of senile dementia.

The study found that specific ratios of brain activity (parietal to cerebellar and parietal to mean cortical activity) could effectively differentiate between patients with Alzheimer's and healthy controls, correlating with the severity of cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging. Hellman, RS., Tikofsky, RS., Collier, BD., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Brain imaging in dementia. [2017]

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

[Brain imaging of Alzheimer' disease: state of the art and perspectives for clinicians]. [2016]

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

Prognostic value of regional cerebral metabolism in patients undergoing dementia evaluation: comparison to a quantifying parameter of subsequent cognitive performance and to prognostic assessment without PET. [2016]

4. Australia pubmed.ncbi.nlm.nih.gov

Regional cerebral blood flow deficits in mild Alzheimer's disease using high resolution single photon emission computerized tomography. [2016]

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

Imaging-based enrichment criteria using deep learning algorithms for efficient clinical trials in mild cognitive impairment. [2018]

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

Automated VOI Analysis in FDDNP PET Using Structural Warping: Validation through Classification of Alzheimer's Disease Patients. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Functional brain imaging with single-photon emission computed tomography in the diagnosis of Alzheimer's disease. [2019]

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

Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease. [2021]

9. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of estimation of brain volume and 2-deoxy-2-(18)F-fluoro-D-glucose metabolism using a novel automated image analysis method: application in Alzheimer's disease. [2016]

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

Alzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging. [2016]