18F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition

Abstract

Background: Florbetaben, a 18F-labeled stilbene derivative (Neuraceq®, formerly known as BAY-949172), is a diagnostic radiopharmaceutical developed to visualize β-amyloid plaques in the brain. Here, we report a pilot study evaluating patients with suspected cardiac amyloidosis for systemic extent of disease.

Methods: We prospectively enrolled nine patients, 61-86 year old (mean ± SD 69.4 ± 8.6), referred from the cardiac amyloid clinic. First, dynamic imaging of the heart was acquired immediately after injection of 222-318.2 MBq (mean ± SD 270.1 ± 33.3) of 18F-florbetaben using the GE SIGNA PET/MRI. This was followed by a whole-body PET/MRI scan 60-146.4 min (mean ± SD 98 ± 33.4) after injection. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Whole-body MRI sequences included MRAC and axial T1-weighted imaging.

Results: High early uptake and delayed high uptake in the left ventricle correlated with amyloid deposition in five patients, while low uptake on early and delayed cardiac imaging was noted in four patients. Cardiac function measurements were successfully obtained in all participants. Areas of increased abnormal 18F-florbetaben accumulation were noted on delayed whole-body imaging in the bone marrow (seven patients), stomach (diffuse in five patients and focal in one patient), brain (five patients), salivary glands (three patients), tongue (three patients), spleen (three patients), skeletal muscles (three patients), ocular muscles (two patients), thyroid (two patients), pleura (two patients), kidneys (two patients), and lungs (two patients).

Conclusions: Whole-body 18F-florbetaben PET/MRI is promising for localization of systemic amyloid deposition. This technique may provide important structural and functional information regarding the organs involved by disease, with potential to guide biopsy and evaluate response to treatment.

Trial registration: Clinicaltrials.gov registration: NCT03119558 .

Keywords: 18F-florbetaben; Amyloid; Cardiac; PET/MR; Systemic.

Conflict of interest statement

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Stanford University Research Compliance Office is the local ethics committee that reviewed and approved the protocol.

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

Competing interests

Sonya Park, Lucia Baratto, Negin Hatami, Praveen Gulaka, Thomas Yohannan, and Ronald Witteles have no conflict of interest. Shreyas Vasanawala, Robert Herfkens, and Andrei Iagaru received institutional research grants from GE Healthcare.

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Figures

Fig. 1

a MIP and b cardiac bed images from participant #2 show intense myocardial 18F-florbetaben uptake, suspicious for amyloid. Intense uptake was also demonstrated in the extraocular muscles, consistent with recent orbital MRI findings that were concerning for amyloid involvement (c). Although such manifestation is rare, intense uptake was noted in the thyroid glands (d). The patient had mild or subclinical hypothyroidism, with low free thyroxine (1.1μg/dl) and upper limit of the TSH normal range (3.85–4.6 mIU/L). Physical examination of the neck also revealed discomfort on palpation

Fig. 2

a MIP and b cardiac bed images from participant #3 with known renal and bone marrow involvement show very low myocardial 18F-florbetaben uptake, but diffuse uptake in the stomach (c). Another interesting finding is the diffuse uptake in the gray matter with loss of gray-white matter separation (d). Given the patient’s age of 70 years, further neurological evaluation was recommended