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ASNC 99M Technetium-Pyrophosphate ASNC PRACTICE POINTS 99mTechnetium-Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis OVERVIEW diagnosis is confirmed by endomyocardial biopsy and typing of amyloid fibrils as needed. The purpose of this document is to identify the critical components involved in performing 99mTechnetium- • Several studies confirm the high sensitivity and pyrophosphate (99mTc-PYP) imaging for the evaluation of specificity of 99mTc-bone compound scintigraphy [99mTc- cardiac transthyretin amyloidosis (ATTR). 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) or PYP(2, 3)] for cardiac ATTR amyloidosis; recent studies highlight the value of DPD and/or PYP in differentiating BACKGROUND cardiac ATTR from AL amyloidosis (4). • The majority of individuals with cardiac amyloidosis • A distinct advantage of 99mTc-PYP imaging, even when have myocardial amyloid deposits formed from echocardiography and CMR are diagnostic for cardiac misfolded light chain (AL) or transthyretin (TTR) proteins. amyloidoisis, is its ability to specifically identify ATTR Diagnosis of amyloidosis and differentiation between cardiac amyloidosis non-invasively and thereby guide the types is important for prognosis, therapy, and patient management (5). genetic counseling. • Cardiac TTR amyloidosis, the focus of this practice PATIENT SELECTION points document, is an under‐diagnosed cause of heart • Individuals with heart failure and unexplained increase failure. in left ventricular wall thickness. • Amyloid derived from wild-type TTR results in a restrictive • African-Americans over the age of 60 years with heart cardiomyopathy, most commonly presenting in men failure, unexplained or with increased left ventricular in their early 70’s onwards, but occasionally seen as wall thickness (>12 mm). young as age 60. Although almost 1 in 4 males > 80 years have some TTR-derived amyloid deposits at • Individuals over the age of 60 years with unexplained autopsy, the clinical significance of a mild degree of heart failure with preserved ejection fraction. deposition is unknown--generally clinical manifestations • Individuals, especially elderly males, with unexplained of heart failure occur once enough amyloid has been neuropathy, bilateral carpal tunnel syndrome or atrial deposited to cause LV wall thickening (1). arrhythmias in the absence of usual risk factors, and • Approximately 3 – 4% among US African Americans signs/symptoms of heart failure. have a common inherited mutation of the TTR • Evaluation of cardiac involvement in individuals with gene (Val122Ile), which produces a restrictive known or suspected familial amyloidosis. cardiomyopathy in a minority, but may contribute to • Diagnosis of cardiac ATTR in individuals with CMR or heart failure in a higher proportion (1). echocardiography consistent with cardiac amyloidosis. • Cardiac amyloidosis should be suspected in individuals • Patients with suspected cardiac ATTR amyloidosis and with heart failure and thickened ventricles with grade 2 contraindications to CMR such as renal insufficiency or or greater diastolic dysfunction on echocardiography an implantable cardiac device (5). or typical findings on cardiac magnetic resonance imaging (CMR; diffuse late gadolinium enhancement, ECV expansion or characteristic T-1 relaxation times); ASNC PRACTICE POINTS 99mTechnetium-Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis OBTAINING THE RADIOTRACER IMAGING PROCEDURE 99m 99m • Tc-PYP is readily available as unit doses from • Commonly used imaging procedures for Tc-PYP commercial radiopharmaceutical distributors or as kits imaging are shown in Table 1. Individual centers can for preparation (TechneScan PYPTM, Mallinkcrodt, St. modify imaging procedures based on local camera Louis, MO). capabilities and expertise. • Kits containing 5 or 30 single-use vials are commercially • Cardiac or chest SPECT and planar images are available. Each 10 ml vial contains 11.9 mg of sodium obtained one hour after injection of 99mTc-PYP using pyrophosphate and 3.2 mg of stannous chloride and the parameters listed in Table 1. If persistent blood pool 4.4 mg of total tin, and this kit is approved for bone, activity is noted on one hour images (e.g., renal failure), cardiac (for the detection of myocardial infarction), delayed images may be obtained at 3 hours. and blood pool (radionuclide ventriculography and • Planar imaging is rapid, simple to perform, and useful for GI bleeding) imaging (see package insert for details of visual interpretation and quantification of the degree of reconstitution of 99m Tc-PYP). myocardial uptake (see image interpretation) by heart • The total body effective dose from 15 mCi of 99mTc-PYP to lung ratio or comparison to rib uptake. is estimated at 3.2 mSv. • SPECT imaging may be helpful to 99m • Tc-DPD is not available for clinical use in the United 1. avoid overlap of bone uptake States. Although there are no large studies directly comparing the agents, the principles in this document 2. distinguish blood pool activity from myocardial apply similarly to 99mTc-DPD and 99mTc-PYP imaging. activity(3) 3. assess the distribution of myocardial 99mTc-PYP TEST PREPARATION uptake in individuals with positive planar scans 99m • No specific test preparation is required. 4. identify Tc-PYP uptake in the interventricular septum (commonly involved in amyloidosis) and 5. quantify the degree of myocardial uptake by comparison to rib uptake. • Whole body planar imaging may be helpful to identify uptake of 99mTc-PYP in the shoulder and hip girdles (a specific sign of systemic ATTR amyloidosis) (6) and should be considered adjunctive and optional in addition to standard cardiac-centered imaging, based on local expertize. • The value of 99mTc-PYP imaging with the newer “cardiac only” SPECT cameras needs further validation (due to inability to accurately display bone and lung 99m Tc-PYP uptake with these systems; see image interpretation section). ASNC PRACTICE POINTS 99mTechnetium-Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis Table 1. Imaging Parameters for Cardiac 99mTc-PYP IMAGE INTERPRETATION Imaging • The anterior and lateral planar images as well as the Imaging procedures Parameters rotating projection images and reconstructed SPECT Preparation No specific preparation. No fasting images are reviewed in standard cardiac imaging required. planes using commercial software. • Myocardial 99mTc-PYP uptake patterns are categorized Scan Rest scan as absent, focal, diffuse or focal on diffuse. Dose of 99mTc-PYP 10-20 mCi intravenously • Scans with focal 99mTc-PYP uptake could represent rib Time between Recommended: 1-hour SPECT fracture or previous myocardial infarction. Following injection and and planar; a myocardial infarction, myocardial 99mTc-PYP uptake acquisition Optional: 3-hour SPECT or planar may be positive for upto 7 days and rarely may remain Imaging parameters persistently positive. Field of view Recommended: Cardiac or chest; Quantifying myocardial 99mTc-PYP Uptake Optional: Wholebody planar There are two approaches to quantification: Image type Recommended: Cardiac or chest 1. Quantitative: myocardial to contralateral lung ratio of SPECT and planar imaging uptake at 1 hour Position Supine • Circular target regions of interest (ROI) are drawn over Energy window 140 keV, 15-20% the heart on the planar images and are mirrored over Collimators Low energy, high resolution the contralateral chest to account for background and Matrix 64 X 64 minimum ribs (see Figure 1). • Total and absolute mean counts are measured in Pixel size 3.5 – 6.5 mm each ROI. A heart to contralateral (H/CL) ratio is Planar imaging specific parameters calculated as the fraction of heart ROI mean counts to Number of views* Anterior, Lateral, and Left Anterior contralateral chest ROI mean counts. Oblique • H/CL ratios of ≥ 1.5 at one hour are classified as ATTR Detector 90 degrees positive and ratios < 1.5 as ATTR negative (4). configuration 2. Semi-quantitative: visual comparison to bone (rib) Image duration 750,000 counts uptake at 3 hours (count based) Cardiac uptake of 99mTc-PYP is evaluated using a semi- Magnification 1.46 quantitative visual scoring method in relation to bone SPECT imaging specific parameters uptake (Table 2 and Figure 2). Based on previously Angular range 360 degrees published results, visual scores of greater than or equal to 2 Detector 180 degrees on planar (2, 3) or SPECT images at 3 hours (6) are classified configuration as ATTR positive, and scores of less than 2 as ATTR negative. ECG gating Off; Nongated imaging While grade 2-3 or H/CL >1.5 uptake is strongly suggestive Number of views/ 40 of TTR amyloidosis, any degree of 99mTc-PYP uptake can detector also be seen in AL amyloidosis, and as such a complete Time per stop 20 seconds evaluation is warranted to exclude this diagnosis. Magnification 1.0 In clinical practice both semi-quantitative visual scoring *Anterior and lateral views can be obtained at the same time using a 90 degree detector configuration; lateral planar views or SPECT imaging may and H/CL are used. help separate sternal from myocardial uptake. ASNC PRACTICE POINTS 99mTechnetium-Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis Table 2. Semi-quantitative Visual Grading of REPORTING Myocardial 99mTc-PYP Uptake by Comparison to The report should include all elements of an ideal Bone(rib) Uptake report as per standard ASNC guidelines. Grade Myocardial 99mTc-PYP Uptake 99m Grade 0 no uptake and normal bone uptake Table 3. Myocardial Tc-PYP Imaging Guideline for Reporting Grade
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