The purpose of this study is to determine if TTR gene carriers have early signs of a type of heart disease called amyloidosis using a new radiotracer dye (iodine-124 evuzamitide, I-124E). Participants will undergo a screening that includes a medical history review and completion of quality-of-life surveys. Once screening is complete, participants will undergo an imaging test called a positron emission tomography (PET) scan combined with computed tomography (PET/CT) to make images of the body. The new radiotracer dye (I-124E, a radioactive contrast) will be used during the PET/CT to make amyloidosis visible in the heart and body.
This will be a cross-sectional cohort study of 50 carriers of pathogenic TTR alleles without HF; 10-race matched non-carrier controls; and 20 patients with ATTR-CA. Participants will undergo standardized, PET/CT direct amyloid imaging assessments with I-124E to test the hypothesis that carriers of pathogenic TTR alleles without HF will have LV%ID intermediate to non-carrier controls and patients with ATTR-CA. This will address the fundamental questions of whether and to what extent cardiac amyloid infiltration is present in carriers of pathogenic TTR alleles prior to ATTR-CA disease onset.
Study Type
OBSERVATIONAL
Enrollment
80
I-124E is a novel amyloidophilic peptide radiotracer that binds via electrostatic interactions to electronegative glycosaminoglycans and amyloid protein fibrils - both are ubiquitous among amyloid deposits. PET/CT I-124E has acceptable dosimetry estimates and is acceptable for whole-body PET/CT imaging. Data from patients with amyloidosis has established that tracer uptake is present in locations of clinically anticipated amyloid deposits and in locations not clinically appreciated, but also consistent with the distribution of amyloid in the human body (e.g. heart, kidney, spleen).
UT Southwestern Medical Center
Dallas, Texas, United States
LV % Injected dose
Evidence of subclinical cardiac amyloid infiltration as measured by PET/CT quantification imaging with I-124E. This will be defined as LV % injected dose (LV%ID = volume of interest \[VOI\] mean activity concentration in the LV X VOI volume / injected activity). LV%ID is an ideal metric to assess cardiac amyloid burden because it is: 1) correlated with validated metrics assessing cardiac amyloid burden; 2) sensitive for detection of early disease (patchy vs. diffuse uptake); and 3) highly repeatable and standardizable to other metrics of radiotracer uptake. LV%ID is adjusted for injected activity, but not for body weight, because the latter is unnecessary for a radiotracer accumulating in the heart and specific organs, not in the whole body.
Time frame: PET/CT Scan Visit
LVFW SUVR, mean
Time frame: PET/CT Scan Visit
LVFW wall SUVR, max
Time frame: PET/CT Scan Visit
IVS SUVR, mean
Time frame: PET/CT Scan Visit
IVS SUVR, max
Time frame: PET/CT Scan Visit
RVFW SUVR, mean
Time frame: PET/CT Scan Visit
RVFW SUVR, max
Time frame: PET/CT Scan Visit
RV % Injected Dose (RV%ID)
Time frame: PET/CT Scan Visit
LV Cardiac Amyloid Activity (CAA)
Time frame: PET/CT Scan Visit
LV Target-to-Background Ratio (TBR)
Time frame: PET/CT Scan Visit
RV Cardiac Amyloid Activity (CAA)
Time frame: PET/CT Scan Visit
RV Target-to-Background Ratio (TBR)
Time frame: PET/CT Scan Visit
Left Atrial Uptake
Time frame: PET/CT Scan Visit
Right Atrial Uptake
Time frame: PET/CT Scan Visit
Liver Uptake
Time frame: PET/CT Scan Visit
Spleen Uptake
Time frame: PET/CT Scan Visit
Kidney Uptake
Time frame: PET/CT Scan Visit
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.