[18F]DPA714 PET Imaging for Brain Inflammation

Overseen By Asim Bag, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Recurrent medulloblastoma, Pregnant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

22 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug [18F]DPA714 for brain inflammation?

Research shows that [18F]DPA714 is effective in monitoring brain inflammation by targeting a protein called TSPO, which is found in higher amounts in activated microglia (immune cells in the brain) in conditions like Alzheimer's and Parkinson's disease. This helps in identifying the best time for anti-inflammatory treatments. ^{1 2 3 4 5}

Is [18F]DPA714 safe for use in humans?

Research on [18F]DPA714, a radiotracer used in PET imaging to study brain inflammation, has been conducted in both animal models and humans. While the studies primarily focus on its effectiveness in imaging neuroinflammation, they do not report any significant safety concerns, suggesting it is generally safe for use in humans. ^{1 2 3 6 7}

How is the drug [18F]DPA714 unique for brain inflammation?

[18F]DPA714 is unique because it is a PET imaging agent that specifically targets the translocator protein (TSPO), which is highly expressed in activated microglia, allowing for non-invasive visualization of neuroinflammation in the brain. This makes it particularly useful for monitoring conditions like Alzheimer's disease and multiple sclerosis, where inflammation plays a key role. ^{1 4 5 8 9}

What is the purpose of this trial?

QARIN 1 is a study of \[18F\]DPA-714 Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy. This TSPO PET, uses a radioactive tracer. An optional MRI (magnetic resonance imaging) will also be performed to monitor brain microstructure damages induced by neuroinflammation. Primary Objectives * Assessment of temporal and regional variability of uptake of translocator protein (TSPO) positron emission tomography (PET) tracer. * Regional variability will be assessed in medial temporal lobe, frontal lobe, and in white matter * Temporal variability will be assessed by scanning each subject four-times: at baseline (before or within 2 weeks of start of radiation therapy), before start of chemotherapy, at 1 year from the initiation of the radiation therapy, and at 1.5-2 years from the initiation of the radiation therapy * Correlation of radiation dose in specific brain regions with radiation induced neuroinflammation as measured by uptake of TSPO PET tracer. Exploratory Objectives * Assessment of radiation-induced brain microstructure injuries (RIBMI) in specific brain regions (medial temporal lobe, frontal lobe, and in white matter) using advanced magnetic resonance imaging (MRI) techniques. * Association of radiation dose with MRI measures of RIBMI in these specific brain regions. * Association of PET measures of RIN with MRI measures of RIBMI. * Association of PET measure of RIN and MRI measures of RIBMI in specific regions of interest (ROI) with specific domain of neuro-cognition. For example, to investigate whether PET measure of RIN and MRI measures of RIBMI in hippocampal ROI have strongest association with episodic memory; whether frontal lobe cortical ROI are associated with attention and executive function. * Association of a novel MRI based technique for assessment of RIN with TSPO PET. * Association of the PET and MRI measure of neuroinflammation within 2- years of completion of radiation with delayed cognitive outcome that will be measured at 3, 4 and 5 years from the completion of radiation

Research Team

Asim Bag, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for individuals at least 8 years old with confirmed medulloblastoma, scheduled for craniospinal irradiation. They must understand and sign consent forms, have specific TSPO gene binding sites (not low-affinity), and not require sedation for PET scans. Pregnant or lactating women and those with certain complications from previous surgeries are excluded.

Inclusion Criteria

I am at least 8 years old.

I have medulloblastoma and will get 36 Gy of radiation to my brain and spine.

My genetic test shows I have a specific variant in the TSPO gene.

Exclusion Criteria

I have complications like a large fluid-filled swelling, bleeding, or fluid buildup in my brain.

My genetic test shows I have low-affinity TSPO binding sites.

I am not breastfeeding as I might be exposed to radiation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo whole brain radiation therapy

2 weeks

1 visit (in-person)

PET Scans

Participants receive 4 PET scans to assess neuroinflammation: at baseline, before chemotherapy, 1 year after radiation, and 1.5-2 years after radiation

2 years

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

3 visits (in-person)

Treatment Details

Interventions

• [18F]DPA714

Trial Overview [18F]DPA714 PET tracer is being tested to measure brain inflammation after whole brain radiation therapy in patients with brain tumors. The study will scan participants' brains multiple times over two years to assess changes in inflammation related to radiation doses received.

Participant Groups

Group I: Participants Experimental Treatment 1 Intervention

Participants who meet the eligibility criteria in the study will receive Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Findings from Research

The study developed a molecular imaging probe, [18F]DPA714, which effectively targets the 18-kDa translocator protein (TSPO) to monitor microglia activation and neuroinflammation in an Alzheimer's disease mouse model, showing a significant increase in uptake in affected brain regions compared to control mice.

Quantitative PET imaging revealed that [18F]DPA714 uptake was significantly higher in the cortex and hippocampus of APP/PS1 mice at 12-13 and 15-16 months of age, indicating its potential utility in determining optimal timing for anti-inflammatory therapies in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging for Dynamically Monitoring Neuroinflammation in APP/PS1 Mouse Model Using [18F]DPA714. Hu, W., Pan, D., Wang, Y., et al.[2020]

In a study involving 24 Parkinson's disease (PD) patients and 28 healthy controls, the use of the radioligand [18F]-DPA714 revealed significantly higher microglial activation in specific brain regions of PD patients, indicating a neuroinflammatory response associated with the disease.

Despite the observed microglial activation, there was no correlation between the level of activation and the severity of motor symptoms or disease duration, suggesting that while neuroinflammation is present, it may not directly influence clinical outcomes in PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. Lavisse, S., Goutal, S., Wimberley, C., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

PET Imaging for Dynamically Monitoring Neuroinflammation in APP/PS1 Mouse Model Using [18F]DPA714. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

[18F]DPA-714: Effect of co-medications, age, sex, BMI and TSPO polymorphism on the human plasma input function. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. [2021]

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

In vivo assessment of neuroinflammation in progressive multiple sclerosis: a proof of concept study with [18F]DPA714 PET. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Optimised GMP-compliant production of [18F]DPA-714 on the Trasis AllinOne module. [2021]

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

[18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

(18)F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy. [2018]

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

PET imaging of retinal inflammation in mice exposed to blue light using [18F]-DPA-714. [2023]

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

PET imaging of retinal inflammation in mice exposed to blue light using [18F]-DPA-714. [2023]