ABC | Volume 114, Nº2, February 2020

Update Update of the Brazilian Guideline on Nuclear Cardiology – 2020 Arq Bras Cardiol. 2020; 114(2):325-429 Table 8 – Indication criteria for myocardial perfusion scintigraphy for assessment of myocardial viability Assessment of myocardial viability Score Accentuated left ventricular dysfunction 9 Eligible for myocardial revascularization 9 viability. It is worth noting that, for diagnostic investigation, patients with intermediate probability of ischemic heart disease are those who most benefit from MPS and that it is rarely appropriate in patients with low probability. 5. Myocardial Perfusion Scintigraphy Methods – types of Cardiovascular Stress 5.1. Radiopharmaceuticals Used to Perform Myocardial Perfusion Scintigraphy In Brazil, the main radiopharmaceuticals available for obtaining images of the myocardium are thallium-201 ( 201 Tl) and those labeled with technetium-99m ( 99m Tc), which mainly include 2-methoxy-isobutyl-isonitrile, known as Sestamibi (or MIBI), and tetrofosmin. Given that these are the most widely used, the specific methods used for acquiring images with them will be presented. Thallium-201 or 201 Tl 17 is a monovalent cation with biological properties analogous to those of potassium. It is both intracellular and absent in scar tissue, and it is thus designated for differentiating ischemic myocardium from fibrosis. It has a physical half-life of 73 hours, and it decays by electron capture to mercury-201 ( 201 Hg), and the photons emitted for imaging are primarily x-rays (of 201 Hg itself) between 68 and 80 kilo- electron volts (keV), in addition to lower quantities of gamma radiation in the energy range of 135 keV and 166 KeV. Upon intravenous injection, initial myocardial uptake is proportional to regional blood flow, depending on the integrity of the cellular membrane. It penetrates the cellular membrane via active transport, involving energy expenditure (Na + /K + ATPase system), with a high first-pass extraction fraction in the myocardium (the proportion of 201 Tl which is extracted from blood and absorbed by myocytes), of around 70% to 85%. Maximumconcentration of thallium-201 in themyocardium occurs approximately 5 minutes after injection, which is generally administered during peak exercise or clinical and/ or electrocardiographic alterations triggered during an ET or a pharmacological test. It presents rapid disappearance or clearance from the intravascular compartment. Following initial distribution of the radioisotope throughout the myocardium, related to blood flow, the phenomenon of redistribution begins 10 to 15 minutes after injection. This is dependent on clearance or washout of thallium-201 from the myocardium, which no longer depends on blood flow but rather on the concentration gradient between myocytes and blood levels. Redistribution of thallium-201 is quicker in normal myocardium than in ischemic myocardium, resulting in different activities in these tissues (differential “washout”). Due to the characteristics described and the ability to evaluate the integrity of the cellular membrane, thallium-201 has the additional property of studying myocardial viability, predominantly related to hibernating myocardium (Figure 1). 18-20 This represents the condition of resting left ventricular dysfunction, resulting from chronic hypoperfusion in myocardial regions where, although the myocytes have remained viable (alive), they have chronically depressed contractile function. Hibernation may also be seen as a “flow-contraction” agreement process, where metabolism remains dependent on residual myocardial flow in a manner sufficient for minimum substrate supply and inhibitory substance removal. Therefore, the condition of hibernation, notwithstanding reduced resting coronary flow, is not necessarily associated with the presence of chronic ischemia, given that oxygen supply and consumption ratio may be preserved. 21,22 Technetium-99m-labeled SESTAMIBI or MIBI (MIBI- 99m Tc): 23,24 The most frequently used marker for myocardial perfusion studies, is 2-methoxy-isobutyl-isonitrile, a stable, lipophilic, cationic compound belonging to the isonitrile family, which has the property of crossing cellular (sarcolemmal) membranes and binding to myocyte mitochondria through the mechanism of passive diffusion, depending on the electrochemical transmembrane gradient. It therefore involves no energy expenditure. It has a lower first-pass extraction fraction in the myocardium than thallium-201, of approximately 60%. 25 It does not expressively present the phenomenon of redistribution, largely remaining retained within mitochondria. This property makes it necessary to deliver 2 separate injections of the radiopharmaceutical, 1 during the resting and 1 during the stress phase. This may be done either on the same day or on different days. As MIBI is not radioactive, it must be labeled with technetium-99m ( 99m Tc), which has a physical half-life of 6 hours and emits gamma photons in the energy range of 140 keV (photopeak). Similarly to thallium-201, initial myocardial uptake is proportional to regional blood flow, depending on the integrity of the cellular membrane. In this manner, a linear relationship is observed between the intravenous dose per gram of myocardium and blood flow per minute (Figure 2), starting at minimal flow ranges of approximately 2.0 to 2.5 milliliters per gram. minute -1 , values normally found in maximum exercise testings. When very high coronary flow are reached, generally over 3.0 mililiters per gram.minute -1 , the linear relationship between this variable and myocardial uptake is lost, with decreased blood extraction of the radiopharmaceutical, in a phenomenon known as “roll off”. 26-28 Nonetheless, owing to higher energy emission (higher photopeak), measured in keV, it presents higher quality images, in comparison with thallium-201. Finally, the elimination of MIBI- 99m Tc takes place through the hepatobiliary system, whereas elimination of thallium-201 is mainly achieved through the renal system. Regarding other isonitriles approved by the FDA for assessment of obstructive CAD, only tetrofosmin, whose properties are similar to those of MIBI- 99m Tc, has been made available for clinical use. 335