Ischemic heart disease is the leading cause of mortality in Australia, accounting for 16 of all registered deaths. (Australian Bureau of statistics, 2009), though the proportion of deaths due to heart disease is declining. This could be due to the fact that our knowledge of diagnosis and treatment of heart disease is improving, and the infrastructure to utilise it is increasing.
Nuclear medicine has become invaluable in the diagnosis of heart disease, allowing for images of the heart which clearly show abnormalities. Explored and compared in this document will be two radiopharmaceuticals used in nuclear medicine to image the cardiac: Tc-99m sestamibi and Tc-99m tetrofosmin.
In cardiac imaging, two different 99m Technetium radiopharmaceuticals are primarily used: Tc-99m sestamibi (trade name Cardiolite) and Tc-99m tetrofosmin (trade name Myoview), along with another radiopharmaceutical, Thallium-201 chloride. (Norio Takashi, 1996)
The Technetium radiopharmaceuticals are both fairly similar in the way they are handled within the body except for some differences in their dosimetry, uptake and retention within the body; Tc-99m Sestamibi compared to Tc-99m tetrofosmin delivers a higher radiation dose to the body (0.5 rads/30mCi compared to 0.2 rads/30mCi), (Ziessman, 2006)(Ravizzini, 2002) the retention of the radiopharmaceutical in the myocardium and other organs also differs slightly, affecting the time at which imaging should commence.
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Both radiopharmaceuticals can also be used in the imaging of the (particularly overactive) parathyroid or the breast.
Both being radiopharmaceuticals derived for Technetium 99m, sestamibi and tetrofosmin have a physical half life of about 6 hours and emit gamma rays that have a mean emission energy of 140.5 KeV. They are both prepared from a kit. (Billerica, 2003)(GE Healthcare, 2006) Sestamibi is Tc-99m connected to 6 isonitrile ligands; MIBI is 2-methoxy isobutyl isonitrile and scans done with sestamibi are often referred to as MIBI scans.
Both Tc-99m sestamibi and Tc-99m tetrofosmin are localized in the myocardium after a rapid clearance from the blood;(Monzen, 2011) they are used in imaging of the myocardium (generally myocardial scintigraphy), rest and stress tests are undertaken with the use of these radiopharmaceuticals to diagnose cardiac disease, artery blockage, post heart attack infarcts, chest pain and ischemia.(Paulo, 1996) The rest and stress tests are taken because infarctions in the heart may only appear when the heart is under stress and can prove the difference between infarcted tissue and ischemia.
Tc-99m sestamibi and Tc-99m tetrofosmin are both administered intravenously, ensuring a prompt uptake in the cardiac muscle. (Monzen, 2011) A single day rest and stress test requires two different dosages; one for each rest and stress which are 370 MBq and 1110 MBq in Tc-99m sestamibi respectively (Paulo, 1996), and 185-444 MBq for rest testing and 555-1221 MBq for stress testing in Tc-99m tetrofosmin.(GE Healthcare, 2006)
When using Tc-99m Sestamibi, imaging is done 15-30 minutes after injection for the stress test and 30-90 minutes after injection for the rest test; whereas for Tc-99m tetrofosmin imaging can be done 5-15 minutes after injection for stress testing and 30 minutes after injection for rest testing. The rest images are produced first, with a four hour delay before the stress images are captured. (Ziessman, 2006) In patients unable to partake in taxing exercise, dobutamine or vasodilator tests are done, where the dobutamine test is preferred. (Abdou, 2005)
The tests are maximal exercise on either a bicycle or a treadmill, and when at maximal level the selected radiopharmaceutical is injected. Precautions taken before the test are to stop medications before the test, particularly beta blockers and also anything containing caffeine, as these may render the results unreliable.
After entering the blood Tc-99m Sestamibi and Tc-99m Tetrofosmin quickly localize in the myocardium due to being a lipophilic cation, the negative potential of the radiopharmaceuticals allows them to be captured in the mitochondrial cells. (Ziessman, 2006) They make use of the Na+/H+ antiporter system to transport to within the cells. However, uptake in the mitochondria mainly occurs in Tc-99m Sestamibi, only a small fraction of Tc-99m tetrofosmin is found in the mitochondria. (Arbab, 1996) These radiopharmaceuticals also localize in the liver and lungs, but are evacuated quickly (due to renal and biliary excretion) whilst maintaining high levels in the myocardium, the elimination from the heart and lungs is said to be quicker in Tc-99m tetrofosmin than Tc-99m sestamibi. This clearance of organs not being imaged allows for clearer imaging of the myocardium due to better contrast. (Paulo, 1996)(Ziessman, 2006)(Kelly, 1993)
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Tc-99m Sestamibi is mainly eliminated through the hepatobiliary system, and within 48 hours approximately 27 and 33 of the injected dose is excreted through urine and faeces respectively. (Ziessman, 2006)(Billerica, 2003) In Tc-99m Tetrofosmin approximately 66 of the injected does is eliminated from the body in the first 48 hours, 40 of which is through urine and 26 through faeces. (GE Healthcare, 2006)
Despite some minute differences in use, the applications of Tc-99m Sestamibi and Tc-99m Tetrofosmin are essentially the same. Tetrofosmin is only relatively new and few studies have been done on its pharmacokinetics, but signs show that in myocardial scintigraphy it might have the edge over sestamibi in terms of patient turnover time and the purity of the drawn dose in terms of efficiency, (Ravizzini, 2002) and image contrast is also slightly better in Tc-99m tetrofosmin compared to Tc-99m sestamibi. (Lind, 1997)
Both of these radiopharmaceuticals have provided much use in the application of imaging the cardiac in patients with heart disease and disorders. Their Tc-99m base and kit production makes them a convenient way to image the heart with little radiation dose to the patient. An increasing availability of nuclear medicine should mean that the diagnosis of heart disease will rise and with that, an improvement in mortality rates amongst those diagnosed. Constant advancement of this field will also produce better results, such as in the youthful Tc-99m Tetrofosmin compared to Tc-99m Sestamibi.