PET Imaging for SARS-CoV-2 Sequelae

Overseen By April Riddle

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Experimental therapies, Illicit substances

Disqualifiers: Pregnancy, Cancer, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to detect brain inflammation in individuals with ongoing symptoms after recovering from COVID-19. The study uses a special molecule, DPA-714 (a radiotracer), which highlights areas of brain inflammation during a scan. Individuals who have had COVID-19 and continue to experience neurological symptoms, such as brain fog or headaches, for at least four weeks may qualify. It also includes healthy volunteers without neurological symptoms for comparison. As an Early Phase 1 trial, this research aims to understand how this new approach works in people, offering participants an opportunity to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, healthy controls should not regularly take over-the-counter anti-inflammatory medication, analgesics (except aspirin), or sleep medication.

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

Research has shown that DPA-714 is generally safe for people. Early studies suggest it works well for PET scans, as it remains stable and spreads evenly in the body, which is important for imaging. No major safety concerns have emerged, indicating it is safe for human use. However, since this research is still in the early stages, more studies are needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses PET imaging with DPA-714 to investigate the long-term effects of COVID-19, specifically in patients experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). Unlike current treatments that mainly focus on managing symptoms, this trial aims to provide a deeper understanding of the underlying biological changes in the brain after COVID-19. DPA-714 targets a specific protein associated with inflammation, potentially offering insights into the neurological impacts of the virus. This approach could pave the way for more effective, targeted therapies in the future.

What evidence suggests that this imaging method is effective for visualizing neuroinflammation in PASC?

Research has shown that DPA-714 effectively detects brain swelling, known as neuroinflammation, by attaching to a protein called TSPO. Studies have found that combining DPA-714 with a tracer like Fluorodeoxyglucose(18F) can clearly reveal inflamed areas in the brain using PET scans. This trial will use DPA-714 to examine brain inflammation in two groups: healthy volunteers and patients meeting the case definition criteria for PASC (Post-Acute Sequelae of SARS-CoV-2 infection). DPA-714 reveals these inflammation patterns, providing insights into ongoing brain changes in these patients. Overall, DPA-714's ability to detect brain inflammation makes it a promising tool for understanding and possibly addressing conditions related to the long-term effects of COVID-19. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who have had neurological symptoms for at least four weeks after recovering from COVID-19, or healthy individuals without neurological issues. Participants must not be pregnant, lactating, severely ill, have blood disorders, autoimmune diseases (except MS), recent substance abuse, other clinical trials involvement or certain abnormal blood test results.

Inclusion Criteria

I had COVID-19 and have had neurological symptoms for at least 4 weeks.

My genetic test shows I have a specific marker (rs6971) for treatment response.

I am either healthy or have long-term effects from COVID-19.

Exclusion Criteria

I haven't needed treatment for an infection in the last month.

Lactation

Contraindication to MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET imaging to visualize and quantify neuroinflammation using Fluorodeoxyglucose(18F)-labeled DPA-714

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DPA-714

Trial Overview The study tests a PET/MRI imaging technique using DPA-714 to detect neuroinflammation in post-COVID patients compared with healthy subjects. It aims to visualize and measure brain inflammation linked to long-term effects of SARS-CoV-2 infection.

How Is the Trial Designed?

Group I: PASC Experimental Treatment 1 Intervention

Patients meeting the case definition criteria for PASC

Group II: Healty Volunteers Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

In a study involving nine patients with suspected PACNS, [18F]DPA-714-PET imaging revealed distinct patterns of microglial activation that could help differentiate PACNS from other conditions, such as ischemic stroke.

The imaging technique showed promise for monitoring treatment response, as evidenced by a reduction in tracer uptake after anti-inflammatory therapy in one patient, indicating its potential utility in managing PACNS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with [18F]DPA-714 TSPO-PET to image inflammation in primary angiitis of the central nervous system. Backhaus, P., Roll, W., Beuker, C., et al.[2021]

The study demonstrated that the radiotracer [18F]DPA714 effectively visualizes inflammation in the lungs of SARS-CoV-2-infected rhesus monkeys, with increased uptake observed in pulmonary lesions and mediastinal lymph nodes as early as 2 days post-infection.

The findings suggest that [18F]DPA714 could serve as a valuable diagnostic tool for monitoring pulmonary inflammation in SARS-CoV-2 and potentially other viral respiratory infections, as it correlates with the activation of immune cells in the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel application of [18F]DPA714 for visualizing the pulmonary inflammation process of SARS-CoV-2-infection in rhesus monkeys (Macaca mulatta). Meijer, L., Böszörményi, KP., Bakker, J., et al.[2022]

Four new analogues of DPA-714 were developed, showing improved affinity and selectivity for the TSPO receptor compared to the original compound, indicating potential for enhanced therapeutic effects.

The selected analogue, DPA-C5yne, demonstrated favorable metabolic stability and was successfully labeled with fluorine-18 for PET imaging, suggesting its utility in studying neuroinflammation in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation and evaluation of novel pyrazolo[1,5-a]pyrimidine acetamides, closely related to DPA-714, as potent ligands for imaging the TSPO 18kDa with PET. Médran-Navarrete, V., Damont, A., Peyronneau, MA., et al.[2016]

This study developed new imaging agents to target ACE2, the receptor that SARS-CoV-2 uses to enter cells, allowing for detailed visualization of ACE2 expression in various organs in both healthy individuals and a patient who recovered from COVID-19.

The imaging revealed unexpected ACE2 uptake in areas like the breast and reproductive system, while showing very low levels in the lungs, providing new insights into the potential pathways of COVID-19 infection and its effects on different body systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular PET/CT Profiling of ACE2 Expression In Vivo: Implications for Infection and Outcome from SARS-CoV-2. Zhu, H., Zhang, H., Zhou, N., et al.[2023]

The new radiotracer [18F]F-DPA was successfully synthesized and showed a high radiochemical purity of over 99%, indicating its potential for reliable use in imaging neuroinflammation.

In comparison to the related radiotracer [18F]DPA-714, [18F]F-DPA demonstrated a significantly higher stability in vivo, with 93.5% of the radioactivity remaining unchanged in the brain, suggesting it may be more effective for imaging neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats. Keller, T., Krzyczmonik, A., Forsback, S., et al.[2023]

Positron emission tomography (PET) is rapidly advancing with new radiopharmaceuticals being developed for various clinical applications, including imaging brain beta amyloid and tumor antigen expression, which could enhance diagnostic capabilities in medicine.

Several multicenter clinical trials are underway to evaluate both proprietary and nonproprietary PET drugs, ensuring they meet safety and efficacy standards before they can be used in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A broad overview of positron emission tomography radiopharmaceuticals and clinical applications: what is new? Vallabhajosula, S., Solnes, L., Vallabhajosula, B.[2016]

The new radioligand [11C]DPA-713 shows improved radiochemical yield (30-38%) and simpler purification methods compared to previous methods, making it more efficient for use in studies of peripheral benzodiazepine receptors.

The synthesis process for [11C]DPA-713 takes only 18-20 minutes, which enhances its suitability for automated production and repeated use in pharmacological and clinical evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate. Thominiaux, C., Dollé, F., James, ML., et al.[2006]

A new series of fluorinated analogues of the TSPO ligand CfO-DPA-714 were developed, showing high affinity and selectivity for the TSPO, with some compounds demonstrating better binding than the original DPA-714.

One promising compound, an N-methyl-N-propyl amide analogue, exhibited similar metabolic stability to CfO-DPA-714 and could be a strong candidate for use as a PET imaging probe for neuroinflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and in vitro characterization of novel fluorinated derivatives of the translocator protein 18 kDa ligand CfO-DPA-714. Cacheux, F., Médran-Navarrete, V., Dollé, F., et al.[2017]

The study utilized 124I-iodo-DPA-713 PET/CT imaging in a hamster model of SARS-CoV-2 infection to successfully visualize and quantify lung inflammation, showing that this imaging tool can effectively highlight areas of activated macrophages in pneumonic lesions.

Results indicated that male hamsters exhibited worse pulmonary disease and higher levels of macrophage activity compared to females, suggesting potential gender differences in immune response to COVID-19, which could inform future therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection. Ruiz-Bedoya, CA., Mota, F., Ordonez, AA., et al.[2023]

DPA-714 is a newly developed radioligand for imaging microglia activation and neuroinflammation using positron emission tomography (PET), providing a valuable tool for studying these processes in vivo.

The creation of a tritium-labeled version of DPA-714 allows for high-resolution imaging and detailed pharmacokinetic studies, enhancing our understanding of its binding properties and potential applications in neuroinflammatory research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient tritiation of the translocator protein (18 kDa) selective ligand DPA-714. Damont, A., Garcia-Argote, S., Buisson, DA., et al.[2015]

In two cases of suspected low-grade glioma, 18F-FDOPA PET scans showed positive results, but histological analysis revealed brain inflammation due to acute disseminated encephalomyelitis (ADEM) and neurosarcoidosis instead of tumors.

The findings suggest that 18F-FDOPA PET scans, typically used to assess tumor activity, may also be useful in studying brain inflammation, highlighting the need for careful interpretation of PET scan results in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-DOPA, a clinically available PET tracer to study brain inflammation? Sala, Q., Metellus, P., Taieb, D., et al.[2016]

The study developed a new PET tracer, 68 Ga-cyc-DX600, which specifically targets the ACE2 protein, allowing for the visualization and quantification of ACE2 fluctuations in various organs after COVID-19 infection in a mouse model.

Using ACE2 PET imaging, researchers found that while ACE2 levels in most organs returned to normal within 15 days post-infection, the brain and genitals showed persistent decreases, indicating potential long-term effects of COVID-19 on these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACE2 PET to reveal the dynamic patterns of ACE2 recovery in an infection model with pseudocorona virus. Li, X., Yin, W., Li, A., et al.[2023]

The study highlights the use of a novel imaging technique, 18F-αvβ6-BP PET/CT, to visualize lung damage in a patient two months after SARS-CoV-2 infection, indicating its potential for monitoring long-term effects of the virus.

In this case, the imaging revealed minimal uptake in healthy lung tissue but increased uptake in damaged areas, suggesting that αvβ6 could serve as a useful biomarker for assessing lung injury post-infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

&#945;v&#946;6-Targeted Molecular PET/CT Imaging of the Lungs After SARS-CoV-2 Infection. Foster, CC., Davis, RA., Hausner, SH., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40441893/

Whole-Body [18F]DPA-714 Kinetic Assessment Using PET ... N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a] pyrimidin-3-yl)acetamide ([18F]DPA-714), which binds with high affinity the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40315803/

Application of the radiopharmaceutical [18F]DPA-714 in ... This mini review explores the application of the radiopharmaceutical [18F]DPA-714 in neuroinflammation studies in post-SARS-CoV-2 patients using ...

3. researchgate.net researchgate.net/publication/392212221_Whole-Body_18FDPA-714_Kinetic_Assessment_Using_PETCT_Scanner_with_Long_Axial_Field_of_View

Whole-Body [18F]DPA-714 Kinetic Assessment Using PET ... Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([(18)F]DPA-714) binds ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/49/5/814

DPA-714, a New Translocator Protein–Specific Ligand 18 F-DPA-714 is a high-affinity radioligand specific for the TSPO. Its suitable in vivo properties and ability to bind to the TSPO with high specificity,

5. researchgate.net researchgate.net/publication/395427778_Varying_Levels_of_Inflammatory_Activity_in_Brain_and_Body_of_Patients_with_Persistent_Fatigue_and_Difficulty_Concentrating_After_COVID-19_A_TSPO_PET_Study

Varying Levels of Inflammatory Activity in Brain and Body ... The PET tracer N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a]pyrimidin-3-yl)acetamide ([18F]DPA-714) binds with high ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35660200/

Novel application of [18F]DPA714 for visualizing the ... This study illustrates that [ 18 F]DPA714 is a valuable radiotracer to visualize SARS-CoV-2-associated pulmonary inflammation, which coincided with ...

7. researchgate.net researchgate.net/publication/339238620_TSPO_imaging-guided_characterization_of_the_immunosuppressive_myeloid_tumor_microenvironment_in_patients_with_malignant_glioma

TSPO imaging-guided characterization of the ... In order to further visualize the immunological response during thermotherapy, we conducted a N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5- ...

8. academia.edu academia.edu/92793191/Initial_evaluation_in_healthy_humans_of_18F_DPA_714_a_potential_PET_biomarker_for_neuroinflammation?uc-sb-sw=2728886

Initial evaluation in healthy humans of [18F]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 ...

9. dumas.ccsd.cnrs.fr dumas.ccsd.cnrs.fr/dumas-04675971v1/file/BAHI_Camille_Pharmacie_2024.pdf

Covid-19, Long-Covid, and the brain: from an acute ... - DUMAS (N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5- a]pyrimidine-3-acetamide ([18F]DPA-714)) and BPND as a comparison parameter,.

10. repository.ubn.ru.nl repository.ubn.ru.nl/bitstream/handle/2066/233891/233891.pdf?sequence=1&isAllowed=y

Exploring interactions between systemic inflammation and the ... Two-tissue compartmental model. 18F-DPA-714. 18-Fluoride labelled N,N- diethyl-2-[4-(3- fluoroethoxy)phenyl]-5,7- dimethylpyrazolo[1,5- a]pyrimidine-3-acetamide.