¹⁸ F-Florbetapir Binds Specifically to Myocardial Light Chain and Transthyretin Amyloid Deposits

Abstract

Background 18F-florbetapir is a promising imaging biomarker for light chain (AL) and transthyretin (ATTR) cardiac amyloidosis. Our aim, using human autopsy myocardial specimens, was to test the hypothesis that 18F-florbetapir binds specifically to myocardial AL and ATTR amyloid deposits. Methods and Results We studied myocardial sections from 30 subjects with autopsy documented AL (N = 10), ATTR (N = 10) and non-amyloid controls (N = 10), using 18F-florbetapir and cold florbetapir compound and digital autoradiography. Total and non-specific binding of 18F-florbetapir was determined using the maximum signal intensity values. Specific binding of 18F-florbetapir was calculated by subtracting non-specific from total binding measurements (in decays per minute/mm2, DPM mm2), and was compared to cardiac structure and function on echocardiography and the histological extent of amyloid deposits. Diffuse or focally increased 18F-florbetapir uptake was noted in all AL and ATTR samples and in none of the control samples. Compared to control samples, mean 18F-florbetapir specific uptake was significantly higher in the amyloid samples (0.94 ± 0.43 vs. 2.00 ± 0.58 DPM/mm2, p < 0.001), and in the AL compared to the ATTR samples (2.48 ± 0.40 vs. 1.52 ± 0.22 DPM/mm2, p < 0.001). The samples from subjects with atypical echocardiographic features of amyloidosis showed quantitatively more intense 18F-florbetapir specific uptake compared to control samples (1.50 ± 0.17 vs. 0.94 ± 0.43 DPM/mm2, p = 0.004), despite smaller amyloid extent than in subjects with typical echocardiograms. Conclusions 18F-florbetapir specifically binds to myocardial AL and ATTR deposits in humans and offers the potential to screen for the two most common types of myocardial amyloid.

Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis

“…Recent studies have shown that it is also taken up in the heart in patients with ATTR-CA and AL-CA (Figure 3, lower right panel). Similar findings have been reported for another beta amyloid imaging agent 11C-PiB 89 . These agents hold promise for absolute quantification of amyloid burden.…”

Transthyretin Cardiac Amyloidosis in Older Adults: Optimizing Cardiac Imaging to the Corresponding Diagnostic and Management Goal

“…(18)F-florbetapir myocardial uptake was elevated in 9/9 patients with CA (4 ATTR-CA, 5 AL) but not in amyloid-negative controls [57]. An autopsy study showed that all myocardial sections of patients with CA (10 ATTR-CA, 10 AL) had elevated uptake of (18)F-florbetapir compared to controls [58]. (18)F-florbetaben also localized to myocardial amyloid fibrils in 10 patients with CA (5 ATTR-CA, 5 AL) with no uptake seen in 4 controls with LVH secondary to longstanding hypertension [59].…”

“…The authors concluded that the presence and type of ATTR mutation may influence (18)Na-F tracer uptake [68]. A recent study of (18)F-florbetapir uptake in myocardial autopsy specimens (10 AL, 10 ATTR, 10 controls) found increased uptake in all CA patients and no controls, with uptake greater in AL than ATTR [58], while another study demonstrated increased liver uptake of (18)F-florbetapir in AL and normal liver uptake in ATTR-CA [69], suggesting that (18)F-florbetapir may preferentially bind AL fibrils.…”

Amyloid Cardiomyopathy

“…3 Physician education, along with now widely accessible assays for diagnosis and monitoring (such as the Freelite ® serum free LC assay) as well as improved cardiac imaging have contributed to the increase in diagnosis. In addition to ultrasound echocardiography and late gadolinium enhancement (LGE) by cardiac MRI, 4 newer imaging modalities with 99m Tc-pyrophosphate 4, 5 and florbetapir 6 have improved detection, monitoring of disease progression, and treatment response in cardiac amyloidosis. With these imaging modalities becoming more widely accessible, it is likely the identification of cardiac amyloidosis will only continue to increase.…”