Tc-HDP quantitative SPECT/CT in transthyretin cardiac amyloid and the development of a reference interval for myocardial uptake in the non-affected population

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Abstract
99mTechnetium-HDP (HDP) bone scans differentiate transthyretin (ATTR) cardiac amyloid from other infiltrative myocardial diseases. These scans are not quantitative and are assessed by comparing myocardial uptake to bone. This study examined whether quantitative HDP SPECT/CT can discriminate individuals with cardiac ATTR from the population without this disease. HDP thoracic xSPECT/CT QUANT (xQUANT) was performed in 29 patients: ATTR cardiac amyloid (n = 6); AL cardiac amyloid (n = 1); other infiltrative myocardial disease (n = 4); no known infiltrative cardiac disease (n = 18). SUVmax measured within volumes of interest for whole heart, ascending aorta blood pool, and specific bones. HDP myocardial uptake calculated as whole heart minus blood pool. The cardiac ATTR group had greater HDP myocardial uptake than those with no known infiltrative disease (p = 0.002). AL and other myocardial diseases had uptake indistinguishable from the group with no known infiltrative cardiac disease. The SUVmaxima were sufficiently similar between individuals without cardiac ATTR that a 99% reference interval for HDP uptake could be calculated, providing an upper limit cut point of SUVmax 1.2. Individuals with cardiac ATTR had SUVmax well above this cut point. Quantitative SPECT/CT can measure HDP myocardial uptake in individuals with normal hearts and those with cardiac ATTR without recourse to comparison with bone. It enables calculation of a reference interval for HDP myocardial uptake in the population without ATTR cardiac amyloid. Using this reference interval single individuals with cardiac ATTR can be accurately discriminated from the non-affected population. This technique uses a NIST traceable calibration source, potentially allowing development of multicentre clinical decision limits. Its role in disease management warrants further assessment.

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