Evaluation of the sensitivity of 18F-NaF PET for the imaging of cardiac amyloidosis

Background: Conventional molecular imaging with bone-seeking radiopharmaceuticals has been shown to be a sensitive test for the detection of transthyretin cardiac amyloidosis (ATTR). The sensitivity is such that the diagnosis of ATTR can be established without biopsy in the presence of cardiac uptake on bone scintigraphy and in the absence of light chains on serum protein electrophoresis (SPEP). To date, little data exists on the utility of ¹⁸F-Sodium fluoride (NaF) positron emission tomography (PET) in subjects with cardiac amyloidosis. The purpose of this study was to assess the ability of NaF-PET to detect ATTR.

Methods: Myocardial perfusion imaging and cardiac NaF-PET of 7 subjects with ATTR, 4 with light chain cardiac amyloidosis (AL), and 4 controls (CTL) were retrospectively reviewed. Dynamic PET/CT was acquired 60 min after intravenous injection of 10mCi of ¹⁸F-NaF for 30 min. The diagnosis of cardiac amyloidosis was confirmed by biopsy in all 4 AL subjects and 3 ATTR subjects. For the remaining 4 ATTR subjects, the diagnosis was established by positive bone scintigraphy with absence of light chains on SPEP. Qualitative interpretation of cardiac NaF uptake and quantitative analyses with average left ventricular standardized uptake value (SUV_mean) and target-to-background-ratios (TBR_mean = SUV_mean/SUV_blood) were performed.

Results: Average SUV_mean were not significantly different between the three groups. Average TBR_mean was significantly increased in subjects with ATTR (0.98 ± 0.09) compared to AL (0.85 ± 0.08, p=0.026) and CTL (0.82 ± 0.07, p=0.020), while SUV_mean was not (ATTR 1.31 ± 0.30, AL 0.84 ± 0.55, CTL 1.29 ± 0.21, p =0.14). Receiver-operator characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.91, with a sensitivity/specificity of 75%/100% using diagnosis based on TBR_mean using a cutoff value of 0.89 for the diagnosis of ATTR. Qualitative interpretation resulted in a sensitivity of 57% and specificity of 100% for ATTR.

Conclusions: While the results of this pilot study suggest that ¹⁸F-NaF PET/CT demonstrates good diagnostic accuracy for ATTR, particularly when using quantitative analysis, its sensitivity is less than the reported sensitivity of established nuclear medicine studies with PYP or DPD. Further studies with direct comparisons to PYP or DPD SPECT are recommended.