Original Article
Quantitation of myocardial 99mTc-HMDP uptake with new SPECT/CT cadmium zinc telluride (CZT) camera in patients with transthyretin-related cardiac amyloidosis: Ready for clinical use?

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Abstract

Background

The aim of this study was to investigate the feasibility of assessing absolute myocardial 99mTc-HMDP uptake in patients with suspected cardiac ATTR using SUV with a whole-body CZT SPECT-CT camera (DNM670CZT).

Methods

Fifteen patients with suspected cardiac ATTR (Perugini ≥ 2) underwent a conventional 99mTc-HMDP planar imaging and a thoracic SPECT/CT using a DNM 670CZT. A control group consisted of 15 patients with negative scintigraphy (Perugini < 2). SUVmax (mg·L−1) and percentage of injected dose (%ID) were calculated in a cardiac volume of interest (VOI) encompassing the left ventricle. VOIs were also placed in the lung, the right pectoris major, and the sternum. A heart-to-lung SUVmax ratio (HLR) was calculated.

Results

All ATTR patients demonstrated an increased cardiac HMDP SUVmax (12.2 ± 3.7 mg·L−1) vs controls (3.5 ± 1.2, P < .0001). Percentage of ID, pectoral uptake and HLR were significantly higher in the ATTR group (1.1 ± 0.3 vs 0.15 ± 0.8, P < .0001; 1.5 ± 0.3 vs 0.9 ± 0.3, P < .0001; 9.7 ± 3 vs 4.3 ± 2.2, P < .0001). Bone uptake was not statistically different between the two groups.

Conclusion

This study demonstrated the feasibility of quantitative 99mTc-HMDP SUVmax measurement using a whole-body SPECT/CT CZT camera in patients with suspected cardiac ATTR.

Introduction

Cardiac amyloidosis is a cause of restrictive cardiomyopathy with preserved ejection fraction associated with amyloid fibrils deposits in the myocardium. Two types of amyloid commonly infiltrate the heart: immunoglobulin light-chain amyloid (AL) and transthyretin-related amyloidosis (ATTR). ATTR encompasses two forms of disease: familial disease with a mutated or variant transthyretin (familial amyloid), and a sporadic, non-genetic disease (wild-type transthyretin). Cardiac ATTR in patients with heart failure is associated with a poor prognosis. Cardiac imaging is currently used for the diagnosis of ATTR, including planar scintigraphy with bone-seeking radiopharmaceuticals,1 cardiac magnetic resonance (CMR) and echocardiography with global longitudinal strain assessment (GLS). Recently, treatment with tafamidis in patients with cardiac ATTR led to a significant reduction in mortality2 and new therapeutic agents that inhibit hepatic synthesis of TTR, stabilize the tetramer, or disrupt fibrils are coming soon.3

The phosphate bone scan can differentiate between ATTR and cardiac AL with a good sensitivity and specificity without difference between the different bone tracers used in clinical routine1,4, 5, 6, 7, 8: hydroxy-dimethylene diphosphonate (HDP), diphosphono-propanodicarboxylic acid (DPD), and pyrophosphate (PYP). The Perugini score is commonly used on planar bone scans to differentiate cardiac ATTR (with high myocardial uptake) from other amyloidosis (AL) or normal patients8 but fails to evaluate amyloid burden and patients’ prognosis.9

Although semi-quantitative methods have been suggested to evaluate the amyloid burden,10 there is a need for quantitative methods for longitudinal assessment of the disease. Using 18F-FDG positron emission tomography (PET), tumor metabolism quantification by standardized uptake value (SUV) is widely validated to assess disease progression and therapeutic response, leading to international harmonization strategies in oncologic imaging.11 Similarly, single photon emission computed tomography (SPECT) quantification in terms of either kBq/cc or SUVs recently became feasible using the new solid-state (CZT) SPECT-CT cameras.12

The aim of this study was to investigate the feasibility of assessing absolute myocardial 99mTc-HMDP uptake in patients with suspected cardiac ATTR using SUV with a new CZT SPECT-CT camera.

Section snippets

Study Population

A phantom study was performed first to validate the system sensitivity, using an anthropomorphic phantom (Data Spectrum Corporation, NC, USA) with cardiac insert, filled with a solution of 99mTc. Mediastinum, liver, and cardiac insert were filled with 10, 41.6 and 2.08 MBq, respectively.

Then, we retrospectively evaluated 30 consecutive patients who underwent bone scintigraphy (99mTc-HMDP) with thoracic SPECT/CT between December 2017 and April 2019 as part of clinical routine for the assessment

Phantom Data

Phantoms acquisition confirmed the good concordance between injected activity and SPECT quantification with a mean difference of 5 and 9%, respectively, in cardiac and liver inserts (Table 1).

Patient Study

Among the 25 patients referred for suspected cardiac amyloidosis, 15 demonstrated a positive planar bone scan (Perugini grade ≥ 2) and constituted the ATTR group. The 10 remaining patients with negative results (Perugini grade 0) were pooled with the 5 patients referred for bone pain and constituted the

Discussion

This study demonstrated the feasibility of quantitative SPECT/CT of HDP myocardial uptake using a new whole-body CZT gamma-camera in patients with suspected cardiac amyloidosis. Our results demonstrated that high SUVs of myocardial uptake clearly identify the patients with ATTR from those with a low probability of disease.

Nuclear medicine quantification has progressed from simple thyroid uptake measurements through to present SUV analysis using PET imaging. With the increase in use PET/CT in

New Knowledge Gained

SUVmax and percentage of injected dose measured with CZT camera are feasible, reliable, and excellent quantitative parameters for cardiac ATTR diagnosis. This new tool has a potential implication in management and follow-up of patient treated by tafamidis for cardiac ATTR amyloidosis.

Conclusion

This study demonstrated the feasibility of 99mTc-HMDP SUVmax measurement using a new whole-body SPECT/CT CZT camera in patients with suspected cardiac ATTR.

The accuracy of quantitative parameters such as SUV max or percentage of injected dose suggest an increase of diagnosis performance of cardiac ATTR with bone scintigraphy and could help to therapy monitoring and prognosis evaluation.

Disclosure

The authors declare that they have no conflict of interest.

Informed Consent

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

Funding

The authors declare that they have no funding.

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All editorial decisions for this article, including selection of reviewers and the final decision, were made by guest editor Nagara Tamaki, MD.

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