Deep Vein Thrombosis, Pulmonary Embolism, Venous Thromboembolism
Conditions
Brief summary
This study aims to investigate a novel positron emission tomography(PET)-probe for imaging of fresh intravascular blood clots in pulmonary embolism (PE) and deep venous thrombosis (DVT).
Detailed description
Venous thromboembolism (VTE) is one of the most common causes of death in the United States, resulting in more than 100,000 deaths annually. Current diagnostic techniques rely on indirect measures of clot for diagnosis and therefore suffer from the problems of both under and overdiagnosis and cannot always be performed on patients with renal failure and lung disease. In this study, we will use the novel fibrin-specific probe 64CU-FBP8 (Copper-64 labeled fibrin binding probe 8) for PET imaging of fresh blood clots in PE and DVT. Our long-term goal is to establish a novel thrombus body scan (TBS) using 64CU-FBP8 for PET imaging to overcome the limitations of indirect venous thromboembolism diagnosis, and, with one single test, provide a total-body assessment of fresh intravascular clot.
Interventions
DRUG64Cu-FBP8
Up to 10 mCi (millicurie) 64Cu-FBP8 will be administered to each subject.
DIAGNOSTIC_TESTPET-CT imaging
All subjects will undergo PET-CT imaging after administration of 64Cu-FBP8.
Sponsors
Peter Caravan
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Subjects with acute pulmonary embolism meeting the inclusion criteria will be enrolled.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older with a clinically significant pulmonary embolus (PE) confirmed by a filling defect in CT angiography (CTA), and * Subjects must receive the radiotracer injection within 72 hours of their diagnosis.
Exclusion criteria
* Subjects \< 18 years of age * Time of expected radiotracer injection \> 72 hours from the time of a positive venous duplex ultrasound or CT- angiogram * Women subjects of childbearing potential who are pregnant, seeking to become pregnant, or have a positive serum pregnancy (beta-HCG) test * Unable to lie flat for 45 minutes as assessed by physical examination and medical history (e.g. back pain, arthritis, dyspnea), * Weight that exceeds the PET camera table limit (300 kg) * The subject will not be enrolled in the study if the radiation exposure for research studies during the prior 12 months, combined with the exposure from this study would exceed 50 mSv (millisievert). * Due to the radiation exposure from imaging studies, all women of childbearing potential will be required to have a negative serum pregnancy test performed prior to any imaging procedures on the same day (if not already done that day). Patients with a positive serum pregnancy test will be excluded. Breast feeding women will also be excluded. * A pre-existing condition or use of a medication including vasopressors and tPA (tissue Plasminogen Activator) that in the opinion of the investigator may place the subject at a substantially increased risk * Hemodynamic instability, including requiring escalating doses of vasopressor medication. * No groups designated as "special vulnerable populations" will be studied. * No exclusions will be made based on race, sex, or ethnic origin. * 64Cu-FBP8 (Copper-64 labeled fibrin binding probe 8) is cleared by the kidneys, patients with eGFR (estimated Glomerular Filtration Rate ) \< 30 will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Location of the Thrombus Within the Lungs | 72 hours | To determine the location of the thrombus regions of interest (ROIs) within the lungs using PET-CT imaging in comparison to the ROI of filling defects on CT-angiogram. |
| Location of Clot Burden Measurements Within the Thigh | 72 hours | To determine the location of the thrombus ROI within the thigh using PET-CT imaging in comparison to the clot on venous duplex ultrasound. |
| Assessment of 64Cu-FBP8 Fibrin Activity in the Pelvic Veins and Upper Extremity | 4 hours | The presence or absence of blood clots as assessed by high 64Cu-FBP8 fibrin activity in the pelvic veins and upper extremities will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Normalized 64Cu-FBP8 Fibrin Activity and Plasma D-dimer | 4 hours | Correlation of the total fibrin activity in the imaged fields, excluding the liver, gallbladder, kidneys and urinary bladder normalized by injected dose with the plasma D-dimer. Outcome measure is the value of the Pearson correlation coefficient . |
| Overall Clot Burden Within the Lungs | 4 hours | Overall clot burden calculated as sum of 64Cu-FBP8 activity within a thrombus ROI(s) within the lungs. This is reported in 4 different ways: 1. TBRmean of the PE which is the ratio of the mean PET signal in the pulmonary embolus (clot) divided by the mean PET signal in the blood pool 2. TBRmax of the PE which is the ratio of the maximum PET signal in the pulmonary embolus (clot) divided by the mean PET signal in the blood pool 3. SUVmean of the PE which is the mean standardized uptake value (SUV) in the pulmonary embolus (clot) 4. SUVmax of the PE which is the maximum standardized uptake value (SUV) in the pulmonary embolus (clot) |
| Overall Clot Burden Within the Thigh | 4 hours | Overall clot burden calculated as sum of 64Cu-FBP8 activity within a thrombus ROI(s) within the thigh. This is reported as: TBRmean of the thrombus which is the ratio of the mean PET signal in the thrombus within the thigh divided by the mean PET signal in the blood pool |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTilo Winkler, PhD
Massachusetts General Hospital
Participant flow
Recruitment details
Participants were recruited between May 2018 and August 2022 based on a PE diagnosis confirmed by CT pulmonary angiogram (CTPA).
Pre-assignment details
Of 6 enrolled participants, 64Cu-FBP8 PET imaging studies were conducted in 5 participants; one participant withdrew before PET imaging.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.8 years |
| D-dimer | 2814 ng/ml |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 6 |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
None listed