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Quantitative [18F]florbetapir PET/CT may identify lung involvement in patients with systemic AL amyloidosis

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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).

Results

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.

Conclusions

[18F]florbetapir PET/CT offers the potential to noninvasively identify pulmonary AL amyloidosis, and its clinical relevance warrants further study.

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Abbreviations

AL:

light chain amyloidosis

ATTR:

transthyretin amyloidosis

FLC:

free light chains

PET/CT:

positron emission tomography computed tomography

RI:

retention index

SUVmax:

maximum standardized uptake value

TBR:

target-to-blood ratio

Vs:

distribution volume of specific binding

HU:

Hounsfield unit

PA:

pulmonary artery

PASP:

pulmonary artery systolic pressure

CMR:

cardiac magnetic resonance imaging

EDV:

end diastolic volume

ESV:

end systolic volume

SV:

stroke volume

EF:

ejection fraction

LV:

left ventricle

RV:

right ventricle

6mwt:

6-min walk test

IQR:

interquartile range

NT-proBNP:

N-terminal pro b-type natriuretic peptide

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Acknowledgments

We are extremely grateful to the study subjects and the study sites for their participation.

Funding

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.

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Authors and Affiliations

  1. Division of Nuclear Medicine, Department of Radiology, Brigham and Women’s Hospital, Boston, MA, USA

    Yiu Ming Khor, Hendrik J. Harms, Marie F. Kijewski, Mi-Ae Park, Matthew Robertson, Hyewon Hyun, Marcelo F. Di Carli & Sharmila Dorbala

  2. Cardiac Amyloidosis Program, Division of Cardiology, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Sarah Cuddy, Rodney H. Falk & Sharmila Dorbala

  3. Division of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA

    Giada Bianchi

  4. Division of Medical Oncology, Memorial Sloan Kettering Medical Center, New York, NY, USA

    Heather Landau

  5. Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Andrew Yee

  6. Amyloidosis Center, Boston University School of Medicine, Boston, MA, USA

    Vaishali Sanchorawala, Frederick L. Ruberg & John Berk

  7. Stanford University Cardiovascular Institute and Cardiovascular Medicine, Stanford Amyloid Center, Stanford, CA, USA

    Ronglih Liao

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  1. Yiu Ming Khor
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Contributions

YMK, SC, HJH, MFK, MAP, MR, HH, and SD were responsible for the study design and performed primary data collection, analysis, and manuscript preparation. FLR, VS, HL, AJY, GB, RL, JB, RHF, and MFD assisted with subject recruitment and/or manuscript editing.

Corresponding author

Correspondence to Sharmila Dorbala.

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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.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Partners Human Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Statement of informed consent was obtained from all individual participants included in the study.

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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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