Technetium 99m sestamibi is a cationic radiotracer with FDA approval as a nuclear myocardial perfusion agent to visualize the blood flow through the heart. Also, sestamibi allows simultaneous assessment of exertional and resting left ventricular ejection fraction. Myocardial perfusion imaging using sestamibi is less invasive than coronary angiography and shows strong evidence in testing for irreversible or reversible ischemia. The American College of Cardiology recommends stress testing using myocardial perfusion imaging for patients with negative biomarkers, nondiagnostic electrocardiography, and chest pain that is not recurrent.[1] Sestamibi is an advantageous agent due to its slow removal from myocardial tissue after cellular uptake with minimal redistribution, allowing for higher quality imaging. Due to its long duration tissue presence and blood flow-dependent uptake, sestamibi also can be used in gated SPECT imaging and to observe the outcome of thrombolytic therapy.[2] This drug is also able to rapidly differentiate ischemic from infarcted tissue when employing gated stress images.[3]

Another FDA-approved indication for sestamibi is in the setting of scintimammography, a complimentary second-line agent in breast imaging for breast cancer when the breasts are mammographically dense, or mammography is inconclusive.[4] Molecular breast imaging has demonstrated an ability to detect 91% of ductal carcinoma in situ lesions and 98% of invasive breast carcinoma.[5] 

Additionally, sestamibi is frequently used in the noninvasive intraoperative localization of hyperfunctioning parathyroid tissues and adenomas in patients with primary hyperparathyroidism.[6]

Finally, a non-FDA approved use of sestamibi is in the detection of multidrug resistance in cancer that is mediated by P-glycoprotein and multidrug resistance-related protein-1.[7] In this setting, low accumulation of sestamibi at the desired tissues indicates the upregulation of these efflux proteins, thus predicting resistance to chemotherapeutic agents that are susceptible to these mechanisms.[8]

Sestamibi is characterized as lipophilic and cationic. It is also characterized as a transport substrate for multidrug resistance-related protein-1 and P-glycoprotein.[9] It has a predilection for tissues that demonstrate both high mitochondrial content and negative plasma membrane potentials.[10] Distribution and delivery into the myocardium, in particular, is dependent on regional blood flow, mitochondrial membrane potential, and mitochondrial content.[11][12] The significantly negative transmembrane potential allows sestamibi to undergo passive diffusion into the mitochondria.[13] Based on these characteristics, tissues with adequate flow and high metabolic activity show sestamibi uptake and accumulation. Furthermore, lack of uptake would be seen in the loss of perfusion and lack of mitochondrial activity, such as during myocardial infarction, or efflux mechanisms, such as in drug-resistant cancers with upregulated P-glycoprotein and multidrug resistance-related protein-1.

To use technetium 99m sestamibi, it must be prepared ahead of time using the water bath method. There are a variety of techniques that have been proposed to heat sestamibi, but the main goal is to heat the compound to a boil. Following this preparation process, there is a six-hour period where the vial must be administered.[14] 

For myocardial perfusion imaging, sestamibi is introduced intravenously, using aseptic technique, in small amounts when the heart is at rest and one minute into maximal stress. Exercise is the preferred way to induce stress, but adenosine receptor agonists, namely dipyridamole, can be used in those with limited exercise capacity.[1] Dipyridamole serves to simulate exercise by inducing coronary vasodilation and is infused for 3-4 minutes.[15] Dobutamine is another agent utilized to bring the heart to maximal stress. Dobutamine is continuously infused up to two minutes following the radiotracer administration. At peak stress, approximately 555 MBq-1.11 (15-30 mCi) is injected. Approximately 30 to 60 minutes after injection, the heart is then imaged using gamma cameras, and images get reconstructed to visualize the regional tracer uptake. The rest images can be performed on a separate day by administering the same dose, 555 MBq-1.11 (15-30 mCi), with gated SPECT 30-60 minutes after injection. [16] Rest images can also be done before stress images by injection 222-370 MBq with imaging 30 minutes later. If rest imaging is done first, the stress imaging can then follow with the combination of dipyridamole stress and 666-1110 MBq of the radiotracer, which is then imaged 30 minutes later.[17] If an area of the myocardium displays better perfusion when the heart is at rest than when it is stressed, then it is indicative of reversible ischemia.[15] In a single study, sestamibi can provide ECG-gated perfusion data to allow the simultaneous evaluation of myocardial perfusion and glucose utilization.[18] 

In preparation for parathyroid surgery, a dose of 740 to 925 megabecquerel of sestamibi is injected intravenously approximately 2.5 to 3 hours before the surgery to localize the adenoma to be removed. Furthermore, to ensure that the radiotracer is not taken up by thyroid parenchyma, the thyroid gland function is inhibited by administering five drops of Lugol's iodine solution every twelve hours four days before the procedure and the day of the procedure. By suppressing the thyroid function, Sestamibi uptake will be isolated to the hyperfunctioning parathyroid adenoma on the day of the surgery.[19]

The standard dosing used in molecular breast imaging is approximately 300 megabecquerel of sestamibi with the use of dual-head cadmium zinc telluride cameras. In this setting, the imaging is gathered immediately after the injection of the radiotracer.[20]

A severe but rare adverse reaction associated with sestamibi injections is allergic reactions. Allergies can range from a mild pruritic maculopapular rash to angioedema and anaphylaxis.[21] Clinicians can prepare for these types of reactions with prophylactic corticosteroids and antihistamines.[22] In general, sestamibi is less radiotoxic relative to other radiopharmaceuticals due to a lesser degree of nuclear localization and unrepaired double-stranded DNA breakage.[23] The majority of side effects are very transient and rarely require any intervention.

Technetium (99mTc) arcitumomab if pregnant or known allergies or hypersensitivity to mouse proteins. Women should not breastfeed for 24 hours after application of the drug. [24]