• Sign Up

Technetium (99mTc) Sestamibi


Technetium (99mTc) Sestamibi

Article Author:
Tony Rizk
Article Editor:
Shivaraj Nagalli
Updated:
7/5/2020 2:58:50 PM
For CME on this topic:
Technetium (99mTc) Sestamibi CME
PubMed Link:
Technetium (99mTc) Sestamibi

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 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]

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, 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.

Administration

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]

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 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, which makes 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, as well as 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]


References

[1] Crownover BK,Bepko JL, Appropriate and safe use of diagnostic imaging. American family physician. 2013 Apr 1;     [PubMed PMID: 23547591]
[2] Javadi H,Porpiranfar MA,Semnani S,Jallalat S,Yavari P,Mogharrabi M,Hooman A,Amini A,Barekat M,Iranpour D,Seyedabadi M,Assadi M,Asli IN, Scintigraphic parameters with emphasis on perfusion appraisal in rest 99mTc-sestamibi SPECT in the recovery of myocardial function after thrombolytic therapy in patients with ST elevation myocardial infarction (STEMI). Perfusion. 2011 Sep     [PubMed PMID: 21593086]
[3] Ghotbi AA,Kjaer A,Nepper-Christensen L,Ahtarovski KA,Lønborg JT,Vejlstrup N,Kyhl K,Christensen TE,Engstrøm T,Kelbæk H,Holmvang L,Bang LE,Ripa RS,Hasbak P, Subacute cardiac rubidium-82 positron emission tomography ({sup}82{/sup}Rb-PET) to assess myocardial area at risk, final infarct size, and myocardial salvage after STEMI. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2018 Jun     [PubMed PMID: 27743299]
[4] Taillefer R, Clinical applications of 99mTc-sestamibi scintimammography. Seminars in nuclear medicine. 2005 Apr;     [PubMed PMID: 15765373]
[5] Huppe AI,Mehta AK,Brem RF, Molecular Breast Imaging: A Comprehensive Review. Seminars in ultrasound, CT, and MR. 2018 Feb     [PubMed PMID: 29317040]
[6] Han CH,Fry CH,Sharma P,Han TS, A clinical perspective of parathyroid hormone related hypercalcaemia. Reviews in endocrine & metabolic disorders. 2019 Dec 3     [PubMed PMID: 31797261]
[7] Gomes CM,Abrunhosa AJ,Pauwels EK,Botelho MF, P-glycoprotein versus MRP1 on transport kinetics of cationic lipophilic substrates: a comparative study using [99mTc]sestamibi and [99mTc]tetrofosmin. Cancer biotherapy     [PubMed PMID: 19409044]
[8] Fox E,Widemann BC,Pastakia D,Chen CC,Yang SX,Cole D,Balis FM, Pharmacokinetic and pharmacodynamic study of tariquidar (XR9576), a P-glycoprotein inhibitor, in combination with doxorubicin, vinorelbine, or docetaxel in children and adolescents with refractory solid tumors. Cancer chemotherapy and pharmacology. 2015 Dec     [PubMed PMID: 26486517]
[9] Gomes CM, Cationic lipophilic radiotracers for functional imaging of multidrug resistance. Current radiopharmaceuticals. 2012 Apr;     [PubMed PMID: 22280111]
[10] Márián T,Balkay L,Szabó G,Krasznai ZT,Hernádi Z,Galuska L,Szabó-Péli J,Esik O,Trón L,Krasznai Z, Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2005 Jun     [PubMed PMID: 15911215]
[11] Arsos G,Kyparos A,Moralidis E,Kyparos D,Georga S,Sotiriadou S,Matziari C,Karakatsanis C, (99m)Tc-sestamibi uptake in rat skeletal muscle and heart: physiological determinants and correlations. Physiological research. 2009;     [PubMed PMID: 18198988]
[12] Safee ZM,Baark F,Waters ECT,Veronese M,Pell VR,Clark JE,Mota F,Livieratos L,Eykyn TR,Blower PJ,Southworth R, Detection of anthracycline-induced cardiotoxicity using perfusion-corrected {sup}99m{/sup}Tc sestamibi SPECT. Scientific reports. 2019 Jan 18;     [PubMed PMID: 30659226]
[13] Kawamoto A,Kato T,Shioi T,Okuda J,Kawashima T,Tamaki Y,Niizuma S,Tanada Y,Takemura G,Narazaki M,Matsuda T,Kimura T, Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure. PloS one. 2015     [PubMed PMID: 25594546]
[14] Doroudi A,Erfani M,Norouzi B,Saadati SM,Kiasat A,Ahmadi F,Etesami B,Baghersad MH, Clinical application of ultrasound for preparation of (99m)Tc-sestamibi complex. Annals of nuclear medicine. 2015 Apr     [PubMed PMID: 25539995]
[15] Patel JJ,Alzahrani T, Myocardial Perfusion Scan . 2020 Jan     [PubMed PMID: 30969594]
[16] Verma B,Singh A, Comparison of Contrast Enhanced Low-Dose Dobutamine Stress Echocardiography with 99mTc-Sestamibi Single-Photon Emission Computed Tomography in Assessment of Myocardial Viability. Open access Macedonian journal of medical sciences. 2019 Apr 30     [PubMed PMID: 31110571]
[17] Wu MC,Tsai CT,Lin HC,Sun FJ,Lin KH, Thallium-201 is comparable to technetium-99m-sestamibi for estimating cardiac function in patients with abnormal myocardial perfusion imaging. The Kaohsiung journal of medical sciences. 2015 Nov     [PubMed PMID: 26678935]
[18] Prvulovich E, Myocardial perfusion scintigraphy. Clinical medicine (London, England). 2006 May-Jun;     [PubMed PMID: 16826859]
[19] Pasta V,Monteleone F,Del Vecchio L,Iacobelli S,Urciuoli P,D'Orazi V, Original technique for preoperative preparation of patients and intraoperative localization of parathyroid adenomas. Il Giornale di chirurgia. 2015 May-Jun     [PubMed PMID: 26188752]
[20] Tao AT,Hruska CB,Conners AL,Hunt KN,Swanson TN,Tran TD,Manduca A,Borges L,Maidment ADA,Lake D,Johnson MP,Carter RE,Rhodes DJ,O'Connor MK, Dose Reduction in Molecular Breast Imaging With a New Image-Processing Algorithm. AJR. American journal of roentgenology. 2020 Jan     [PubMed PMID: 31593516]
[21] Makaryus JN,Makaryus AN,Azer V,Diamond JA, Angioedema after injection of Tc-99m sestamibi tracer during adenosine nuclear stress testing. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2008 Jul-Aug;     [PubMed PMID: 18674710]
[22] Hesse B,Vinberg N,Mosbech H, Exanthema after a stress Tc-99m sestamibi study: continue with a rest sestamibi study? Clinical physiology and functional imaging. 2011 May;     [PubMed PMID: 21470366]
[23] Maucksch U,Runge R,Wunderlich G,Freudenberg R,Naumann A,Kotzerke J, Comparison of the radiotoxicity of the {sup}99m{/sup}Tc-labeled compounds {sup}99m{/sup}Tc-pertechnetate, {sup}99m{/sup}Tc-HMPAO and {sup}99m{/sup}Tc-MIBI. International journal of radiation biology. 2016 Nov;     [PubMed PMID: 27117205]
[24] Sandevska E,Gjorcheva DP,Vavlukis M,Sandevski A,Kafedziska I,Krstik-Damjanovska L,Majstorov V,Jovanovska-Perchinkova S,Guchev F,Kostova N, Myocardial Perfusion Abnormalities in Young and Premenopausal Women with Systemic Lupus Erythematosus, Detected with 99MTC MIBI Myocardial Perfusion Scintigraphy - Prevalence and Correlation with Proatherogenic Factors. Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki). 2018 Dec 1     [PubMed PMID: 30864359]
[25] Technetium Tc 99m Sestamibi 2006;     [PubMed PMID: 30000641]
[26] Thomas GS,Miyamoto MI,Morello AP 3rd,Majmundar H,Thomas JJ,Sampson CH,Hachamovitch R,Shaw LJ, Technetium 99m sestamibi myocardial perfusion imaging predicts clinical outcome in the community outpatient setting. The Nuclear Utility in the Community (NUC) Study. Journal of the American College of Cardiology. 2004 Jan 21;     [PubMed PMID: 14736440]
[27] Boiten HJ,van Domburg RT,Valkema R,Schinkel AF, Eleven-year prognostic value of dobutamine stress (99m)Tc-sestamibi myocardial perfusion imaging in patients with limited exercise capacity. The American journal of cardiology. 2015 Apr 1;     [PubMed PMID: 25661571]
[28] Reilly DJ,Chew GL,Eckhaus J,Smoll NR,Farrell SG, Outcomes for minimally invasive parathyroidectomy: widening inclusion criteria based on preoperative imaging results. ANZ journal of surgery. 2016 Sep;     [PubMed PMID: 25345711]
[29] Guo C,Zhang C,Liu J,Tong L,Huang G, Is Tc-99m sestamibi scintimammography useful in the prediction of neoadjuvant chemotherapy responses in breast cancer? A systematic review and meta-analysis. Nuclear medicine communications. 2016 Jul;     [PubMed PMID: 26974314]