[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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study brain inflammation in individuals with medulloblastoma undergoing whole-brain radiation therapy. The researchers focus on using a special PET scan with a radioactive tracer, [18F]DPA714, to observe changes in inflammation over time and across different brain areas. Participants diagnosed with medulloblastoma and scheduled for radiation treatment may be suitable candidates. The primary goal is to understand the effects of radiation on the brain and its potential relationship to changes in cognitive skills over time. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing valuable insights into its efficacy.

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 prior data suggests that this PET imaging technique is safe for assessing brain inflammation?

Research has shown that [18F]DPA-714 PET imaging is generally safe for people. Early studies indicate that this tracer, used to detect brain inflammation, mostly attaches only to the intended areas, which is a positive sign for safety.

In healthy individuals, initial tests found that [18F]DPA-714 effectively identifies brain inflammation without causing major side effects. Other studies have also used this imaging in patients with brain conditions, further supporting its safety.

While the safety data is encouraging, discussing any concerns with a doctor before joining a clinical trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for brain inflammation rely on medications that reduce symptoms over time. However, [18F]DPA714 offers a new approach by using a PET imaging technique to directly visualize and quantify neuroinflammation in the brain. This imaging method targets the Translocation Protein (TSPO), providing a more detailed and accurate assessment of brain inflammation. Researchers are excited because this could lead to earlier detection and more personalized treatment plans, potentially improving outcomes for patients undergoing whole brain radiation therapy.

What evidence suggests that [18F]DPA714 PET imaging is effective for assessing brain inflammation?

Research shows that [18F]DPA714 is a promising tool for detecting brain inflammation. Studies have found that it remains stable and spreads well throughout the body, making it a reliable marker for observing changes in the brain. In animal studies, [18F]DPA714 PET imaging successfully identified brain inflammation. In this trial, participants will receive [18F]DPA714 PET imaging to assess brain neuroinflammation following whole brain radiation therapy. This ability to highlight changes is particularly useful after treatments like radiation therapy and could help researchers understand how brain inflammation affects thinking and memory over time. ^{6 7 8 9 10}

Who Is on the Research Team?

Asim Bag, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10663012/

[18F]DPA-714 PET Imaging in the Presurgical Evaluation of ... The additional value of [18F]DPA-714 PET seemed to be greater in patients with normal brain MRI or with neocortical EZ (especially if insula is involved).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0969805111002459

Initial evaluation in healthy humans of [ 18 F]DPA-714, a ... This initial study in humans shows that [ 18 F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06467773

TSPO-PET/MRI in Surveillance of Neuroinflammation in the ... This study aims to explore the application of 18F-DPA-714 PET/MR in the early diagnosis, treatment evaluation, and prognosis of central nervous system ...

4. ppmi-info.org ppmi-info.org/sites/default/files/docs/PPMI%20019%20DPA-714%20PET%20Imaging%20Study%20Protocol%20v1.1_27_Sep2023.pdf

Longitudinal TSPO PET imaging with [18F]DPA-714 in ... STUDY OUTCOMES. The primary study outcome will be the regional brain binding of [18F]DPA-714 PET imaging assessment of brain synaptic density ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4722075/

Evaluation of PET Imaging Performance of the TSPO ... [18F]DPA-714 PET imaging was performed in 8 mouse and rat models of breast and brain cancer and 4 mouse and rat models of muscular and bowel inflammation.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9296394/

Evaluation of [18F]F-DPA PET for Detecting Microglial ... Ex vivo PET imaging of the removed spinal cord showed [18F]F-DPA accumulation in the inflammation site, which was immunohistochemically ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06280742

Study of Neuroinflammation in Multiple Sclerosis by PET ... The PET-MR procedure involves TSPO PET using [18F]-DPA-714 in conjunction with 3T MRI for both MS patients and healthy volunteers. Gadoteric acid is ...

8. link.springer.com link.springer.com/article/10.1007/s11307-021-01646-5

Direct Comparison of [18F]F-DPA with [18F]DPA-714 and ... According to several animal studies, [18F]DPA-714 is better for PET imaging than [11C]PK11195, due to its low nonspecific binding in the brain ...

9. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2014.08.105

Imaging neuroinflammation in Alzheimer's disease and other ... Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol. 2012; 39: 570–578.

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022510X25001352

Application of the radiopharmaceutical [ 18 F]DPA-714 in ... 18 F]DPA-714 is a valuable tool for research and treatment of neuroinflammation in post-SARS-CoV-2 patients, with significant implications for the development ...