Continuing Education Activity

Technetium 99m sestamibi (MIBI), also known as 99m Tc-methoxy isobutyl isonitrile, is a radiopharmaceutical used to evaluate pathology within the cardiac, breast, and parathyroid tissues. Sestamibi is part of the radioactive diagnostic agents class of medications, characterized as a lipophilic cationic radiotracer. This activity illustrates the indications, mechanism of action, and contraindications for sestamibi as a valuable diagnostic agent. Furthermore, this activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent for members of the interprofessional team in the diagnosis of patients with cardiac conditions, hyperparathyroidism, and breast cancer.

Objectives:

• Summarize the mechanism of action of technetium 99m sestamibi.
• Identify the indications for the use of technetium 99m sestamibi.
• Outline the common adverse events associated with technetium 99m sestamibi.
• Describe the importance of collaboration and communication amongst the interprofessional team to ensure appropriate selection of candidates for the use of technetium 99m sestamibi to enhance the delivery of care and improve outcomes for patients experiencing cardiovascular events.

Indications

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 for 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]

Mechanism of Action

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, are 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.

Administration

To use technetium 99m sestamibi, it must be prepared ahead of time using the water bath method. A variety of techniques 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 to 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 to 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 to 30 mCi), with gated SPECT 30-60 minutes after injection. [16] Rest images can also be done before stress images by injection 222 to 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 to 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, it indicates 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 using dual-head cadmium zinc telluride cameras. In this setting, the imaging is gathered immediately after the injection of the radiotracer.[20]

Adverse Effects

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.

Contraindications

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

Toxicity

The average effective radiation dose of myocardial perfusion imaging is approximately 12 millisieverts, which is equivalent to the radiation dose of performing 923 posteroanterior chest radiographs. Sestamibi is superior to thallium in terms of toxicity profile due to the lower radiation dose. It is comparable to the radiation dose of coronary CT angiography while being less invasive.[1] The effective half-life of sestamibi is approximately 5.4 hours, and the physical half-life is approximately 6 hours. The principal photon energy of gamma emission is 140.5 keV.[25] The risk of toxicity with this agent is very low, making it a favorable tracer for myocardial perfusion imaging. 

Enhancing Healthcare Team Outcomes

The proper use of technetium 99m sestamibi requires an interprofessional team of healthcare professionals that includes a nurse, pharmacist, and a number of physicians in different specialties. Although improper usage of sestamibi in itself is not very dangerous, adverse clinical outcomes manifest secondary to missed diagnoses leading to insufficient medical management. With proper utilization, myocardial perfusion defects can be accurately identified, thus reducing the morbidity and mortality of cardiovascular events. Patients who present with chest pain need rapid diagnostic stratification to rule out myocardial infarction. In the outpatient setting, a nurse can inject the radiotracer in a patient presenting with chest pain to be later imaged by the cardiologist. The prognostic information derived from the proper utilization of sestamibi includes predicting clinical outcomes in the outpatient setting and determining stress parameters for very long-term outcomes in patients with limited exercise capacity.[26][27] [Level 3]

The American College of Radiology rated myocardial perfusion imaging with an appropriateness criteria score of eight on the nine-point scale for the setting of intermediate and or high probability of myocardial infarction.[1] The radiotracer injection with a concomitant ultrasound study for preoperative parathyroid localization by the radiologist and nuclear medicine physician followed by confirmation by the surgeon results in an increased number of successful minimally invasive parathyroidectomy procedures to effectively treat primary hyperparathyroidism.[28] [Level 3] Lastly, a nurse can inject the radiotracer for the radiologists to identify the presence of breast malignancy and also to assist the oncologist in predicting the response to neoadjuvant chemotherapy.[29] [Level 1] In all these cases, the proper dosage, storage, and administration of sestamibi should be done after consultation with the hospital pharmacist to ensure correct application and preparation. Only by working as an interprofessional team can the maximal diagnostic benefit be derived from the use of sestamibi. [Level 5]