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?

The purpose of the study is to evaluate a new radiotracer called 64Cu-FBP8 for PET-MR imaging of thrombosis. The tracer has the potential of detecting thrombosis anywhere in the body, for instance in the left atrial appendage of patients with atrial fibrillation, and thereby may provide a non-invasive alternative to the current standard-of-care methods.

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.

Is 64Cu-FBP8 safe for use in humans?

The research indicates that 64Cu-FBP8 has been tested in rats for imaging blood clots, and there is ongoing work to translate these findings into human trials, suggesting preliminary safety evaluations are underway. ^{1 2 3 4 5}

How does the drug used in PET Imaging for Blood Clots differ from other treatments?

The drug used in PET Imaging for Blood Clots, known as 64Cu-FBP8, is unique because it specifically targets fibrin, a key component of blood clots, allowing for precise imaging of thrombi (blood clots) throughout the body using PET scans. This approach is different from traditional methods that may not provide detailed information about the clot's composition or location. ^{1 2 3 4 5}

What data supports the effectiveness of the drug 64Cu-FBP8 for imaging blood clots?

Research shows that 64Cu-FBP8 is effective in detecting blood clots in rats, as it binds specifically to fibrin, a key component of clots. This drug has shown promise in imaging clots in different parts of the body, which could help in diagnosing conditions like deep vein thrombosis and pulmonary embolism. ^{1 2 3 5 6}

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

Patient not requiring mechanical ventilation

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.

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]

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]

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]

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 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 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. United States 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Peptide-based fibrin-targeting probes for thrombus imaging. [2018]

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

Fibrin-targeted PET probes for the detection of thrombi. [2022]

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

Multisite Thrombus Imaging and Fibrin Content Estimation With a Single Whole-Body PET Scan in Rats. [2022]

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

Effect of Chelate Type and Radioisotope on the Imaging Efficacy of 4 Fibrin-Specific PET Probes. [2022]

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

Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance. [2023]