1. Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology
18Fluorine Sodium Fluoride Positron Emission Tomography, a Potential Biomarker of Transthyretin Cardiac Amyloidosis
Rachelle Morgenstern MPH1, Randy Yeh2 MD, Adam Castano MD MS1, Mathew S. Maurer MD3 and Sabahat Bokhari MD1 
1 Nuclear Cardiology Lab, Columbia University College of Physicians and Surgeons, New York, NY
1 Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY
3 Center for Advanced Center for Heart Failure, Columbia University College of Physicians and Surgeons, New York, NY
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2. Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology
BACKGROUND
1- Cardiac amyloidosis is a rare but underdiagnosed disease, the pathogenesis of which involves the infiltration of insoluble protein fibrils in the myocardium that can cause arrhythmias, heart failure, and cardiac death. 2- Non-invasive imaging modalities, including magnetic resonance imaging (MRI), echocardiography, and nuclear imaging, have been used to assess cardiac amyloidosis. 3- Positron Emission Tomography (PET) imaging provides high resolution scans which can be used for the visualization of protein deposits and absolute quantification of radiotracer uptake. 4- The radiotracer 18Fluorine sodium fluoride (18F-NaF), is readily available in a variety of centers and may be a viable tracer to visualize and quantify amyloid fibril deposition in patients with cardiac amyloidosis using PET imaging.
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3. METHODS Study type: Prospective, case-control, pilot study.
Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology
METHODS
Study type:
Prospective, case-control, pilot study.
Study subjects: Cases had biopsy proven light chain cardiac amyloidosis (AL) (n=2) or transthyretin-related cardiac amyloidosis (ATTR-CA) (n=5) and prospectively underwent 18F-NaF PET/Computed Tomography with Attenuation Correction (CTAC). Patients who previously underwent 18F-NaF PET/CTAC imaging to screen for prostate cancer were retrospectively assessed as controls (n=5).
Study endpoints:
Primary end point(s): Myocardial 18F-NaF uptake in cases and controls assessed visually and quantitatively using standard uptake values (SUV), calculated as radiotracer uptake within the manually defined LV contours normalized for injected dose and patient weight, for the entire myocardium.
Secondary end point: Myocardial 18F-NaF uptake measured as SUV in a 17-segment cardiac model.
Study variables: Demographic characteristics, clinical characteristics, SUV for the entire myocardium, and SUV for each segment in a 17-segment cardiac model.
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4. Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology
RESULTS
Figure 2. 18Fluorine-labeled sodium fluoride (18F-NaF) localization and distribution are shown qualitatively and quantitatively using standard uptake values (SUV). (A, B) Qualitatively, there was moderate diffuse myocardial uptake of 18F-NaF in a representative scan of a patient with biopsy-proven ATTRwt, predominantly in the inferior wall of the heart. SUV for the entire myocardium (SUVm) was 1.7 and was heterogeneous according to segment. (C, D) Similarly, there was qualitative uptake of 18F-NaF in a representative scan from an ATTRm patient, visually and quantitatively (SUVm = 1.4) slightly less than that of ATTRwt patients. (E, F) In a representative scan from an AL patient, minimal background activity is visualized and corresponds to a SUVm (1.0). 18F-NaF uptake is absent in a representative scan of a control subject with a corroborating SUVm (0.7), significantly lower than that of ATTR-CA patients but comparable to AL patients.
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5. Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology
RESULTS
Figure 3. Distribution of 18fluorine labeled-sodium fluoride uptake in cases and controls using standard uptake values for the entire myocardium (SUVm), was analyzed using 2-Sided Wilcoxon rank-sum tests. SUVm was different between amyloid patients (1.4 ( ) and controls (0.8 ( )) (p=0.018) (A). SUVm of controls did not differ significantly from that of patients with light chain cardiac amyloidosis (AL) (0.95 ( )) (p=0.434), but did significantly differ from transthyretin cardiac amyloidosis patients (ATTR-CA) (1.5 ( )) (p=0.012). SUVm of ATTR-CA patients was 1.5*SUVm of AL patients, and statistically approached significance (p=0.078), but did not meet it likely due to decreased sample size. Accordingly, results suggests that the differences in SUVm between cases and controls is driven by patients with ATTR-CA.
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6. Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology
CONCLUSIONS
1- Results from our study demonstrate that 18F-NaF PET/CTAC was an effective modality for imaging ATTR-CA but not AL patients.
2- Qualitative and quantitative assessments demonstrated myocardial 18F-NaF uptake in ATTR-CA patients was significant and differed from controls and patients with AL.
3- Using semi-automatic quantification with a 17-segment cardiac model, the degree of myocardial radiotracer uptake differed across cardiac segments, indicating that transthyretin fibril deposition may vary according to cardiac region.
4- Considering, the strength of PET/CTAC imaging as a true quantitative methodology, further research efforts utilizing 18F-NaF as a biomarker of transthyretin amyloid deposition may be useful for the care and management of patients with ATTR-CA.
Copyright American Society of Nuclear Cardiology