Usefulness of 18F-sodium fluoride PET/MR imaging for the assessment of cardiac amyloidosis.

Objectives: Cardiac amyloidosis exists in two predominant forms called acquired monoclonal immunoglobulin light-chain (AL) and transthyretin-related (ATTR). Their differentiation is a real diagnostic challenge for treatment management and prognosis of patient. Magnetic resonance (MR) imaging is increasingly used to aid in the diagnosis of amyloid alongside histology on the basis of characteristic appearances on late Gadolinium enhancement (LGE) but cannot distinguish ATTR and Al forms. Several series have showed that single-photon emission computed tomography using bone 99mTc-bisphosphonate tracers preferentially bind ATTR versus AL deposit in the myocardium. Our aim was to use 18F-Sodium Fluroide (18F-NaF) positron emission tomography (PET) bone tracer in hybrid PET/MR imaging to aid in both the diagnosis of cardiac amyloidosis and differentiation of ATTR and AL forms within a single low radiation scan.

Methods: Consecutive patients with biopsy-proven ATTR or AL cardiac amyloidosis and as many control subjects without clinical suspicion of amyloid disease were included in this study (ClinicalTrials.gov Identifier: NCT01418313). All patients underwent simultaneous 90min PET/MR (Biograph^TM mMR, Siemens, Erlangen, Germany) scans, beginning 10min after IV injection of 370MBq of 18F-NaF. A late 60min scan time window, starting at 40min after injection, was selected for providing a better PET contrast in myocardium after dynamic analysis of the 90min PET data. The selected data were reconstructed using a 3D breath-hold Dixon MR attenuation correction map. The MR protocol included LGE sequences, pre- and post-contrast T1 mapping. Maximal target-to-background ratio (TBRmax) was recorded, defined as maximal myocardial FDG uptake (SUVmax) corrected for blood pool activity (SUVmean) from right atrium. Mean TBRmax in ATTR, AL and control subjects were compared using a Student t-test. The institutional review board approved the study (GCO#01-1032) and all patients gave written informed consent.

Results: Eighteen patients (61.3 ± 10.5 yo, 12M/6F) were prospectively recruited, comprising 6 ATTR, 3 AL and 9 control subjects. All amyloid patients had characteristic LGE appearances. Mean TBRmax were respectively 1.29 ± 0.31, 0.77 ± 0.06 and 0.68 ± 0.03 in ATTR, AL and control subjects. Mean TBRmax was significantly higher in ATTR than in AL patients (p=0.028) and in control subjects (p=0.0001). Mean TBRmax was significantly higher in AL patients than in control subjects (p=0.046). A TBRmax threshold of 0.85 appeared to differentiate all patients as having ATTR amyloidosis. There was no significant difference in terms of pre-contrast (p=0.48) and post-contrast T1 mapping (p=0.57) between ATTR and AL patients.

Conclusion: These results showed the potential of NaF-PET/MR to diagnose cardiac amyloidosis and to differentiate ATTR and AL forms, confirming our preliminary published results (Trivieri et al. J Am Coll Cardiol 2016). Research Support: This work was supported by National Institutes of Health (NIH) grants NIH/NHLBI R01HL071021 (to Dr. Fayad) and NIH 5T32HL007824-18 (to Dr. Trivieri), and by British Heart Foundation grants SS/CH/09/002/26360, FS/13/77/30488, SS/CH/09/002/2636, FS/14/78/31020, CH/09/002 (to Dr. Dweck).