Technetium (99mTc) sestamibi
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|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Excretion||Fecal (33%) and renal (27%)|
|Mol. mass||777.852 g/mol|
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Technetium (99mTc) sestamibi (INN) (commonly sestamibi; USP: technetium Tc 99m sestamibi; trade name Cardiolite) is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex consisting of the radioisotope technetium-99m bound to six (sesta=6) methoxyisobutylisonitrile (MIBI) ligands. The anion is not defined. The generic drug became available late September 2008. A scan of a patient using MIBI is commonly known as a "MIBI scan."
Cardiolite is mainly used to image the myocardium (heart muscle). It is also used in the work-up of primary hyperparathyroidism to identify parathyroid adenomas, for radioguided surgery of the parathyroid and in the work-up of possible breast cancer.
The history of Nuclear cardiology began in 1927 when Dr. Herrmann Blumgart developed the first method for measuring cardiac strength by injecting subjects with a radioactive compound known as Radium C (Bi214) . The substance was injected into the venous system and traveled through the right heart into the lungs, then into the left heart and out into the arterial system where it was then detected through a cloud chamber. The cloud chamber represented a primitive scintillation counter which could measure radioactivity. Measured over time, this sequential acquisition of radioactivity produced what was known as "circulation time". The longer the "circulation time", the weaker the heart. Blumgart's emphasis was twofold. First, radioactive substances could be used to determine cardiac physiology (function) and should be done so with the least amount of radioactivity necessary to do so. Secondly, to accomplish this task, one needs to obtain multiple counts over time.
For decades no substantial work was done until 1959. Dr. Richard Gorlin 's work on "resting" studies of the heart and nitroglycerin emphasized several points. First, like Blumgart, he emphasized that evaluation of cardiac function required multiple measurements of change over time and these measurements must be performed under same state conditions, without changing the function of the heart in between measurements. If one is to evaluate ischemia (reductions in coronary blood flow resulting from coronary artery disease) then individuals must be studied under "stress" conditions and comparisons require "stress-stress" comparisons. Similarly, if tissue damage (heart attack, myocardial infarction, cardiac stunning or hibernation) is to be determined, this is done under "resting" conditions. Rest-stress comparisons do not yield adequate determination of either ischemia nor infarction. By 1963, Dr. William Bruce, aware of the tendency of people with coronary artery disease to experience angina (cardiac chest discomfort) during exercise, developed the first standardized method of "stressing" the heart, where serial measurements of changes in blood pressure, heart rate and electrocardiographic (ECG/EKG) changes could be measured under "stress-stress" conditions. By 1965 Dr. William Love demonstrated that the cumbersome cloud chamber could be replaced by a Geiger counter, which was more practical to use. However, Love had expressed the same concern as many of his colleagues, namely that there were no suitable radioisotopes available for human use in the clinical setting.
Use of Thallium-201
By the mid 1970s, scientists and clinicians alike began using thallium-201 as the radioisotope of choice for human studies. Individuals could be placed on a treadmill and be "stressed" by the "Bruce protocol" and when near peak performance, could be injected with thallium-201. The isotope required exercise for an additional minute to enhance circulation of the isotope. Using nuclear cameras of the day and given the limitations of Tl-201, the first "stress" image could not be taken until 1 hour after "stress". In keeping with the concept of comparison images, the second "stress" image was taken 4 hours after "stress" and compared with the first. The movement of Tl-201 reflected differences in tissue delivery (blood flow) and function (mitochondrial activity). The relatively long half-life of Tl-201 (72 hours) forced doctors to use relatively small (2-3 mCi) doses of Tl-201, albeit relatively large dose exposure and tissue effects (20 mSv). The poor quality images resulted in the search for isotopes which would produce better results.
The introduction of Technetium-99m isotopes
By the late 1980s, two different compounds containing technetium-99m were introduced: teboroxime  and sestamibi. The utilization of Tc-99m would allow higher doses (up to 30 mCi) due to the shorter physical (6 hours) half life of Tc-99m. This would result in more decay, more scintillation and more information for the nuclear cameras to measure and turn into better pictures for the clinician to interpret.
Cardiac imaging (MIBI scan)
A MIBI scan or sestamibi scan is now a common method of cardiac imaging. Technetium (99mTc) sestamibi is a lipophilic cation which, when injected intravenously into a patient, distributes in the myocardium proportionally to the myocardial blood flow. Single photon emission computed tomography (SPECT) imaging of the heart is performed using a gamma camera to detect the gamma rays emitted by the technetium-99m as it decays. Two sets of images are acquired. For one set, 99mTc MIBI is injected while the patient is at rest and then the myocardium is imaged. In the second set, the patient is stressed either by exercising on a treadmill or pharmacologically. The drug is injected at peak stress and then imaging is performed. The resulting two sets of images are compared with each other to distinguish ischemic from infarcted areas of the myocardium. This imaging technique is limited to being correct only 76% of the time. The problem lies in choosing which images to compare to what. Resting images as discussed by Gorlin in the late 1950s are useful only for detecting tissue damage, while stress images provide evidence of coronary artery (ischemia) disease. Consequently, comparing these two images has led to many errors in disease detection and to results which fail to match results seen when the arteries of the heart are looked at using coronary angiography. Recent[when?] studies taking 10 years to complete have demonstrated (infra) that comparing stress-stress images can accurately detect ischemia while rest-rest images can accurately differentiate between dead (infarcted) heart (myocardium) tissue and stunned or hibernating myocardium.
Sestamibi was previously thought to not redistribute because earlier studies looked at individuals with no ischemia. This was an error unsupported by Maublant, Crane, Li, Fleming and Ono. The Fleming-Harrington Redistribution Wash-in Washout (FHRWW) or redistribution rate for such individuals without heart disease was approximately 15–20%, with half of this (10%) the result of technetium-99m decay over 55 minutes. It is now known that sestamibi redistributes more under conditions of ischemia with the most critical disease only detectable by "wash-in" where the Black Hole effect of cardiology is detected by a delay in uptake by the tracer (both sestamibi and myoview) during the first few minutes. Failure to image the heart at 5 minutes after stress leads to these individuals being missed. Specifically, the count activity increases at 60 minutes compared with 5-minute images when critical narrowing of coronary arteries is present.
With dipyridamole (Persantine MIBI scan)
When combined with the drug dipyridamole, a brand name of which is Persantine, a MIBI scan is often referred to as a Persantine MIBI scan.
In primary hyperparathyroidism, one or more of the four parathyroid glands either develops a benign tumor called an adenoma or undergoes hypertrophy as a result of homeostatic dysregulation. The parathyroid gland takes up 99mTc MIBI following an intravenous injection, and the patient's neck is imaged with a gamma camera to show the location of all glands. A second image is obtained after a washout time (approximately 2 hours), and mitochondria in the oxyphil cells of the abnormal glands retaining the 99mTc are seen with the gamma camera. This imaging method will detect 75 to 90 percent of abnormal parathyroid glands in primary hyperparathyroidism. An otolaryngologist or an endocrine surgeon can then perform a directed parathyroidectomy (less invasive than traditional surgery) to remove the abnormal gland.
Radioguided surgery of the parathyroids
Following administration, 99mTc MIBI collects in overactive parathyroid glands. During surgery, the surgeon can use a probe sensitive to gamma rays to locate the overactive parathyroid before removing it.
The drug is also used in the evaluation of breast nodules. Malignant breast tissues concentrate 99mTc MIBI to a much greater extent and more frequently than benign disease. As such, limited characterization of breast anomalies is possible. Scintimammography has a high specificity for breast cancer, and has a sensitivity of 66% based on positive biopsy compared to mammography and ultrasound with a 29% positive biopsy.
More recently, breast radiologists administer lower doses of Tc99m-sestamibi (approximately 4-8mCi) for Molecular Breast Imaging (MBI) scans which results in a high sensitivity (91%) and high specificity (93%) for breast cancer detection. It however carries a greater risk of causing cancer making it not appropriate for general breast cancer screening in patients.
The last reference listed is in reference to a 20mCi dose, which is given with the Dilon single-head system, which requires a higher dose since only one camera is utilized (meaning the camera needs to be able to see through more tissue). A 4-8mCi dose, which is used in the other two commercially available MBI systems is essentially equivalent to a mammogram (4mCi) or a tomosynthesis exam (8mCi).
Since even small doses of ionizing radiation are believed to carry some risk of causing cancer, MBI is usually limited to women with dense breast tissue, which often results in inconclusive mammograms. Researchers continue to devote their time to improving the technology, changing scan parameters, and reducing dose to patients."
- Blumgart HL, Yens OC. Studies on the velocity of blood flow: I. The method utilized. J Clin Investigation 1927;4:1-13.
- Love, William D. (1965). "Isotope Technics in Clinical Cardiology" 32. pp. 309–315. doi:10.1161/01.CIR.32.2.309. Retrieved 27 April 2012.
- Gorlin R, Brachfeld N, MacLeod C. and Bopp P. Effect of nitroglycerin on the coronary circulation in patients with coronary artery disease or increased left ventricular work. Circulation 1959;19:705-18.
- Love WD. (1965) Isotope Technics in Clinical Cardiology. Circulation 32:309-15.
- Bisi, G; Sciagrà, R, Santoro, GM, Cerisano, G, Vella, A, Zerauschek, F and Fazzini, PF (July 1992). "Myocardial scintigraphy with Tc-99m-teboroxime: its feasibility and the evaluation of its diagnostic reliability. A comparison with thallium-201 and coronary angiography". Giornale italiano di cardiologia 22 (7): 795–805. PMID 1473653.
- Untch, B. R.; Barfield, M. E.; Bason, J.; Olson Jr, J. A. (2007). "Minimally Invasive Radio-guided Surgery for Primary Hyperparathyroidism". Annals of Surgical Oncology 14 (12): 3401–3402. doi:10.1245/s10434-007-9519-0. PMID 17899291.
- Rhodes DJ, Hruska CB, Phillips SW, Whaley DH, O'Connor MK. (January 2011). "Dedicated dual-head gamma imaging for breast cancer screening in women with mammographically dense breasts.". Radiology 258 (1): 106–18. doi:10.1148/radiol.10100625. PMID 21045179.
- Moadel, RM (May 2011). "Breast cancer imaging devices.". Seminars in nuclear medicine 41 (3): 229–41. doi:10.1053/j.semnuclmed.2010.12.005. PMID 21440698.
- O'Connor MK, Li H, Rhodes DJ, Hruska CB, Clancy CB, Vetter RJ. (December 2010). "Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast.". Medical Physics 37 (12): 6187–98. doi:10.1118/1.3512759. PMID 21302775.
- "Development of radiation dose reduction techniques for cadmium zinc telluride detectors in molecular breast imaging". Proc SPIE. Retrieved 10 December 2013.
- Cardiolite official page
- Molecular Breast Imaging
- The Sestamibi Scan for Hyperparathyroidism on: Parathyroid.com