The clinical diagnosis of pulmonary involvement in individuals with systemic AL amyloidosis remains challenging. [18F]florbetapir imaging has previously identified AL amyloid deposits in the heart and extra-cardiac organs. The aim of this study is to determine quantitative [18F]florbetapir pulmonary kinetics to identify pulmonary involvement in individuals with systemic AL amyloidosis.
We prospectively enrolled 58 subjects with biopsy-proven AL amyloidosis and 9 control subjects (5 without amyloidosis and 4 with ATTR cardiac amyloidosis). Pulmonary [18F]florbetapir uptake was evaluated visually and quantified as distribution volume of specific binding (Vs) derived from compartmental analysis and simpler semiquantitative metrics of maximum standardized uptake values (SUVmax), retention index (RI), and target-to-blood ratio (TBR).
On visual analysis, pulmonary tracer uptake was absent in most AL subjects (40/58, 69%); 12% (7/58) of AL subjects demonstrated intense bilateral homogeneous tracer uptake. In this group, compared to the control group, Vs (median Vs 30-fold higher, 9.79 vs. 0.26, p < 0.001), TBR (median TBR 12.0 vs. 1.71, p < 0.001), and RI (median RI 0.310 vs. 0.033, p < 0.001) were substantially higher. Notably, the AL group without visually apparent pulmonary [18F]florbetapir uptake also demonstrated a > 3-fold higher Vs compared to the control group (median 0.99 vs. 0.26, p < 0.001). Vs was independently related to left ventricular SUVmax, a marker of cardiac AL deposition, but not to ejection fraction, a marker of cardiac dysfunction. Also, intense [18F]florbetapir lung uptake was not related to [11C]acetate lung uptake, suggesting that intense [18F]florbetapir lung uptake represents AL amyloidosis rather than heart failure.
[18F]florbetapir PET/CT offers the potential to noninvasively identify pulmonary AL amyloidosis, and its clinical relevance warrants further study.
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light chain amyloidosis
free light chains
positron emission tomography computed tomography
maximum standardized uptake value
distribution volume of specific binding
pulmonary artery systolic pressure
cardiac magnetic resonance imaging
end diastolic volume
end systolic volume
6-min walk test
N-terminal pro b-type natriuretic peptide
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We are extremely grateful to the study subjects and the study sites for their participation.
SD and RF are supported by NIH RO1 grant (RO1 HL 130563); SD and RL are supported by American Heart Association Grant (AHA 16 CSA 2888 0004). HL receives support from NIH/NCI Cancer Center Support Grant P30 CA008748. MDC is supported by Spectrum Dynamics and Gilead.
Conflict of interest
HH is a working owner of MedTrace Pharma. MDC has received consulting fees from Sanofi and GE Healthcare. HL has received consulting fees from Celgene, Takeda, Janssen, Prothena, Pfizer, and Juno and research support from Amgen, Spectrum, and Takeda. VS has received research support from Takeda, Celgene, Janssen, and Prothena and is on the scientific advisory board for Caleum Biosciences. FLR has received consulting fees from Pfizer, GlaxoSmithKline, and Caleum Biosciences and research support from Eidos Therapeutics. RHF has received consulting fees from Ionis Pharmaceuticals and Alnylam Pharmaceuticals and research funding from GlaxoSmithKline. SD has received consulting fees from Pfizer, GE Healthcare, and AAA and research grants from Pfizer. YMK declares that she has no conflict of interest. SC declares that she has no conflict of interest. MFK declares that she has no conflict of interest. MAP declares that she has no conflict of interest. MR declares that he has no conflict of interest. HH declares that she has no conflict of interest. GB declares that she has no conflict of interest. AJY declares that he has no conflict of interest. RL declares that she has no conflict of interest. JB declares that he has no conflict of interest.
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Khor, Y.M., Cuddy, S., Harms, H.J. et al. Quantitative [18F]florbetapir PET/CT may identify lung involvement in patients with systemic AL amyloidosis. Eur J Nucl Med Mol Imaging 47, 1998–2009 (2020). https://doi.org/10.1007/s00259-019-04627-7
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