PET Imaging for Blood Clots

Overseen By Anne L Philip, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must be taking: Anticoagulants

Must not be taking: Thrombolytics

Disqualifiers: Under 18, Pacemaker, Pregnant, others

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

Compensation: Varies

Number of Visits: 1

165 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to find blood clots using a special tracer, 64Cu-FBP8 (a radiotracer), and a PET-MR scan. The goal is to determine if this method can safely and accurately detect blood clots throughout the body, potentially providing an easier alternative to current tests. Participants are divided into groups, including those with cancer, COVID-19, atrial fibrillation (irregular heartbeat), and other clotting conditions. Individuals with a history of atrial fibrillation, a positive COVID-19 test, a cancer diagnosis, or a high likelihood of having a blood clot may be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative imaging method.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on an anticoagulation regimen and it changes after a TEE (a heart scan), there is a 72-hour waiting period before PET imaging.

What prior data suggests that 64Cu-FBP8 is safe for PET-MR imaging of thrombosis?

Research has shown that the new radiotracer, 64Cu-FBP8, is safe for humans. Studies have found it has low radiation levels and is quickly eliminated through the kidneys, meaning it doesn't remain in the body long—a positive sign for safety.

In earlier tests with people, the radiotracer successfully detected blood clots without causing serious side effects. These results suggest that 64Cu-FBP8 is generally well-tolerated. However, like any new treatment, more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using 64Cu-FBP8 for blood clots because it offers a new way to detect thrombi using PET imaging. Unlike traditional imaging methods, which might not always clearly identify clots, 64Cu-FBP8 binds directly to fibrin, a key component of blood clots, allowing for more precise imaging. This targeted approach can potentially lead to earlier and more accurate diagnosis of thrombotic conditions. Moreover, the use of PET imaging with 64Cu-FBP8 could provide detailed insights into clot size and location, helping tailor more effective treatment plans for patients.

What evidence suggests that 64Cu-FBP8 is effective for detecting thrombosis?

Research has shown that 64Cu-FBP8 is a promising tool for detecting blood clots. Studies have demonstrated that this substance can successfully identify clots in the lungs and veins, particularly after conditions like deep vein thrombosis (DVT) or pulmonary embolism (PE). In this trial, participants—including cancer patients, COVID-19 patients, patients with other thrombotic conditions, atrial fibrillation patients, and healthy volunteers—will receive an injection of 64Cu-FBP8 to evaluate its effectiveness in detecting thrombi. The tracer attaches to fibrin, a protein in blood clots, which helps highlight the clots during imaging. It also exits the body quickly, reducing unnecessary radiation exposure. With these features, 64Cu-FBP8 could offer a non-invasive method to detect clots anywhere in the body. ^{1 6 7 8 9}

Who Is on the Research Team?

Ciprian Catana, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with atrial fibrillation or cancer, who've had a recent test confirming no changes in their blood clotting status, and have tested positive for COVID-19 within the last month. It's not for those under 18, pregnant or breastfeeding women, people over certain weight limits, those with electrical implants like pacemakers, or anyone unable to undergo PET/MR imaging.

Inclusion Criteria

You have a confirmed blood clot shown on an ultrasound or CT scan, or have a high chance of having a blood clot based on a blood test called D-dimer.

Patient not requiring mechanical ventilation

I have a history of irregular heartbeats.

Exclusion Criteria

Your heart rate is consistently too fast (over 120 beats per minute) or too slow (under 50 beats per minute).

I've had chest pain recently but underwent a stress test or coronary angiography afterwards.

You have been exposed to too much radiation in the past year according to the Radiology Department's guidelines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Safety Assessment

Participants are injected with [64Cu]FBP8 and undergo PET/MR imaging to evaluate safety, whole body distribution, metabolism, pharmacokinetics, and radiation burden.

48 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging, including blood collection and electrocardiogram assessments.

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 64Cu-FBP8

Trial Overview [64Cu]FBP8 is being tested as a new radiotracer in PET-MR scans to detect thrombosis (blood clots) non-invasively. The study will include additional procedures like blood collection and electrocardiograms to assess the tracer's effectiveness compared to standard methods.

How Is the Trial Designed?

Group I: Other Thrombotic Condition Patients Experimental Treatment 2 Interventions

Fifty (50) patients with other thrombotic conditions will be injected with \[64Cu\]FBP8 and imaged for thrombi in the body.

Group II: Cancer Patients Experimental Treatment 2 Interventions

Thirty (30) cancer patients will be injected with \[64Cu\]FBP8 and imaged for thrombi in the body.

Group III: COVID-19 Patients Experimental Treatment 2 Interventions

Thirty (30) COVID-19 patients will be injected with \[64Cu\]FBP8 and imaged for thrombi in the body.

Group IV: Atrial Fibrillation Patients Experimental Treatment 2 Interventions

Thirty-five (35) patients with LAA thrombus documented by TEE will be injected with \[64Cu\]FBP8 and imaged for LAA thrombus with MR-PET. The TEE studies in these patients will be part of their routine clinical care. Thirty-five (35) patients with atrial fibrillation and negative TEE will be injected with \[64Cu\]FBP8 and imaged for LAA thrombus. Forty (40) patients with atrial fibrillation who are scheduled for TEE in the upcoming 14 days will be injected with \[64Cu\]FBP8 and imaged for LAA thrombus.

Group V: Healthy Volunteers Active Control 4 Interventions

Twenty (20) healthy adult subjects will be injected with \[64Cu\]FBP8 to establish the safety, whole body distribution, metabolism, pharmacokinetics, and radiation burden of the probe. All subjects will be imaged using PET/MR. Healthy subjects will undergo blood collection before, during, and after the scan. Healthy subjects will also undergo electrocardiogram before and after the scan. An interim review of the data will be conducted after the first six subjects receive the study agent and complete all safety assessments.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The novel PET probe (64)Cu-FBP8 effectively detects deep vein thrombosis (DVT) and pulmonary embolism (PE) in rats, showing significant differences in uptake between thrombus and background tissues, which supports its potential use in clinical settings.

The biodistribution studies indicate that (64)Cu-FBP8 has a rapid clearance from the body, with low radiation exposure (0.021 mSv/MBq for males and 0.027 mSv/MBq for females), making it a safe option for human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Dosimetry of the Fibrin-Binding Probe ⁶⁴Cu-FBP8 and Its Feasibility for PET Imaging of Deep Vein Thrombosis and Pulmonary Embolism in Rats. Blasi, F., Oliveira, BL., Rietz, TA., et al.[2018]

Three new fibrin-targeted PET probes (FBP1, FBP2, FBP3) were developed and evaluated for their ability to detect thrombi, showing high specificity and effectiveness in a rat model of carotid artery thrombosis.

FBP1 and FBP2 demonstrated significantly higher uptake in thrombus-containing arteries compared to the contralateral arteries, indicating their potential as effective tools for noninvasive thrombus imaging, confirmed by hybrid MR-PET imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibrin-targeted PET probes for the detection of thrombi. Ciesienski, KL., Yang, Y., Ay, I., et al.[2022]

Recent advancements in non-invasive molecular imaging techniques have shown promise in detecting thrombosis by targeting fibrin, a key component in thrombus formation, across various disease models and in patients.

The fibrin-binding PET probe [64Cu]FBP8 has successfully progressed from preclinical studies to human trials, highlighting its potential for improving the diagnosis and monitoring of thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide-based fibrin-targeting probes for thrombus imaging. Oliveira, BL., Caravan, P.[2018]

The newly developed PET probes FBP8 and FBP9, which use (64)Cu, demonstrated significantly improved metabolic stability and high thrombus-to-background ratios, making them effective for in vivo thrombus imaging in a rat model.

In contrast, the Al(18)F derivatives FBP10 and FBP11 showed lower stability and less effective imaging results, highlighting the importance of probe stability for accurate thrombus visualization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Chelate Type and Radioisotope on the Imaging Efficacy of 4 Fibrin-Specific PET Probes. Blasi, F., Oliveira, BL., Rietz, TA., et al.[2022]

The study demonstrated that (64)Cu-FBP8-PET imaging can accurately detect both arterial and venous thrombi in a whole-body approach, achieving a high localization accuracy of 97.6% in a rat model with 32 subjects.

This imaging technique not only identifies thrombus locations but also allows for the estimation of fibrin content, revealing that younger clots have higher fibrin levels compared to older ones, which could inform therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats. Blasi, F., Oliveira, BL., Rietz, TA., et al.[2022]

The novel imaging technique using [64Cu]FBP8 with PET/CMR can accurately detect and characterize thrombus in the left atrial appendage (LAA), achieving 100% sensitivity and 84% specificity compared to traditional transesophageal echocardiography (TEE) in a study involving 24 patients with atrial fibrillation.

This method not only identifies the presence of thrombi but also provides insights into their biological properties, such as fibrin and methemoglobin content, which could enhance the understanding of thrombus characteristics and improve stroke prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance. Izquierdo-Garcia, D., Désogère, P., Philip, AL., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11230308/

Dosimetry of [64Cu]FBP8: a fibrin-binding PET probe This study demonstrates the following properties of the [ 64 Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4762685/

Radiation dosimetry of the fibrin-binding probe 64Cu-FBP8 ... We tested the feasibility of 64 Cu-FBP8-PET to detect source thrombi and culprit emboli after deep vein thrombosis and pulmonary embolism (DVT-PE).

3. jnm.snmjournals.org jnm.snmjournals.org/content/early/2015/05/14/jnumed.115.157982

Radiation dosimetry of the fibrin-binding probe 64 Cu-FBP8 ... Results: 64Cu-FBP8-PET imaging detected the location of lung emboli and venous thrombi after DVT-PE, revealing significant differences in ...

4. researchgate.net researchgate.net/publication/381823815_Dosimetry_of_64CuFBP8_a_fibrin-binding_PET_probe

Dosimetry of [64Cu]FBP8: a fibrin-binding PET probe Conclusions: This study demonstrates the following properties of the [64Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/56/7/1088/tab-figures-data

Article Figures & Data - Journal of Nuclear Medicine Radiation Dosimetry of the Fibrin-Binding Probe 64Cu-FBP8 and Its Feasibility for PET Imaging of Deep Vein Thrombosis and Pulmonary Embolism in ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1936878X21006343

Detection and Characterization of Thrombosis in Humans ... We show in this first-in-human study that PET/CMR of the fibrin-binding PET probe [64Cu]FBP8 can detect acute to subacute LAA thrombi with a sensitivity of 100% ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/56/7/1088

Radiation Dosimetry of the Fibrin-Binding Probe 64 Cu ... We tested the feasibility of 64 Cu-FBP8 PET to detect source thrombi and culprit emboli after deep vein thrombosis and pulmonary embolism (DVT-PE).

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39633070/

First-in-human Evaluation of Safety and Dosimetry of [64Cu ... This study demonstrates the following properties of the [ 64 Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; ...

9. ahajournals.org ahajournals.org/doi/abs/10.1161/ATVBAHA.115.306055

Multisite Thrombus Imaging and Fibrin Content Estimation ... Conclusions—. We demonstrated that 64Cu-FBP8-PET is a feasible approach for whole-body thrombus detection and that molecular imaging of fibrin ...