Continuing Education Activity

Thallium-201 is a radiopharmaceutical agent used in the diagnosis of coronary artery disease and parathyroid hyperactivity. Other useful applications for a thallium-201 scan, like tumor diagnosis and olfacto-scintigraphy, are being explored and have shown promising results in various studies. This activity reviews the indications, mechanism of action, administration, adverse effects, monitoring, toxicity, and enhancement of health care outcomes for Thallium-201 as a valuable diagnostic agent in the clinical setting as pertinent for members of the interprofessional team in the evaluation and diagnosis of coronary artery disease and related conditions in patients.

Objectives:

• Identify the mechanism of action of thallium-201.
• Describe the potential adverse effects of thallium-201.
• Review the possibility of toxicity with thallium-201.
• Outline the importance of collaboration and communication amongst the interprofessional team to enhance care coordination for patients receiving thallium-201 for scintigraphy.

Indications

Thallium-201 is an isotope of the element thallium, which has been accepted by the Food and Drug Administration (FDA) for use as a radiopharmaceutical in nuclear medicine scans.[1] Indications for the thallium-201 scan are as follows:

FDA Approved Indications

Myocardial imaging: One of its principal uses is in myocardial imaging. It can help to differentiate between ischemic and infarcted myocardium by comparing the scans at rest and stress (exercise or pharmacological stress). Ischemic myocardium shows decreased uptake only at stress, whereas infarcted/scarred myocardium shows fixed defects present at rest as well as stress. [2] Thallium-201 myocardial perfusion scan is especially very useful in the following: 

• Diagnosis of symptomatic and asymptomatic coronary artery disease.[3]
• Screening of non-specific results on the exercise EKG test.[2]
• Determination of risk before non-cardiac surgery.[3] There is a high risk of cardiac complications during vascular surgeries, like abdominal aortic aneurysm repair. Hence, ischemia, if shown by the scan, must be addressed before the surgery.[4]
• Determination of risk after an event of myocardial infarction.[3]
• Determination of risk before and after revascularization procedures.[5][3]

In addition to evaluating myocardial perfusion, thallium-201 has an additional advantage over other nuclear scans in its property of redistribution, so it can also assess the viability of the myocardium, thus separating ischemic myocardium from scar tissue.[6][1][7] In contrast to normal myocardial cells, poorly perfused areas show reduced uptake and slow clearance.[8]

Parathyroid imaging: Thallium-201 has been used in parathyroid imaging in patients with hyperplasias and adenomas.[9][10] Studies show that thallium-201 can be used in addition to USG for parathyroid imaging prior to surgery.[11][12] However, technetium (Tc) based scintigraphy is superior to thallium-201 for imaging parathyroid abnormalities.[13][14]

Non-FDA Approved Indications

Primary CNS lymphoma (PCNSL): Thallium-201 is useful in distinguishing toxoplasmosis from PCNSL in HIV patients. In current practice, HIV patients with intracranial masses are treated empirically for toxoplasmosis; this increases mortality and morbidity due to delay in diagnosis and treatment. Thallium-201 is collected in tumor cells but not normal or dead cells; thus, it helps diagnose PCNSL. There has been a proposal that the thallium-201 SPECT (single-photon emission computerized tomography) scan in conjunction with cerebrospinal fluid PCR for EBV (Epstein-Barr virus) be used to diagnose PCNSL to initiate empiric radiotherapy.[15][16] However, thallium-201 alone in the diagnosis of PCNSL is not recommended.[17]

Pulmonary Kaposi sarcoma: Thallium-201 scintigraphy is useful to diagnose the Kaposi sarcoma of the lungs without mucocutaneous involvement, which is a challenging diagnosis. A positive thallium-201 scan is used in conjunction with a negative gallium scan to make the diagnosis.[18][19]

Neoplasms: Thallium-201 is also very useful in diagnosing various tumors of the body, including pulmonary, thyroid, lymphomas, and breast.  Other uses include estimating the response of solid tumors like osteosarcoma to chemotherapy.[20] It has also been useful in the diagnosis of pediatric brain and soft tissue neoplasms.[21][22]

Olfacto-scintigraphy: Thallium-201 administered via nasal route can be additionally used to image and assess the integrity of the olfactory pathway, which can be useful in patients with reduced olfaction or following head trauma.[23][24][25][26]

Thyroid imaging: In some studies of patients with toxic goiter, thallium-201 proved to be a useful diagnostic tool to view the normal surrounding thyroid cells, which was not possible with other imaging modalities like Tc-99m and I-123.[27][28]

Mechanism of Action

Thallium-201 is analogous to potassium in structure and uses the sodium-potassium pumps to get into cells of various organs.[2] It has a half-life of about 73 hours and decays to mercury-201, releasing low energy gamma rays and X-rays, making it a useful radiopharmaceutical for scintigraphy.[29][30] Thallium-201 is taken up in the myocytes in about 5 to 15 minutes after injection. It is cleared out from the body via the kidneys, thus reducing the artifacts in the bowel and gallbladder usually present in other myocardial scans.[30][31] These pharmacokinetic properties of thallium-201 make it suitable for myocardial perfusion imaging (MPI). In contrast to normally perfused myocardial cells, ischemic cells show delayed uptake. Thus the initial images help assess the perfusion, while the delayed images help evaluate the viability of the myocardium.[32]

Administration

Different imaging protocols are available for thallium-201 based myocardial perfusion imaging. The more common stress-rest protocols begin with stress imaging 15 minutes after injection of thallium-201, followed by rest imaging after 2.5 to 4 hours, and finally a redistribution imaging 24 hours later.[30] While the best protocol is not yet established, it should be selected and administered according to individual patient characteristics and habitus, associated medical conditions, and indications for the study. However, there is a common consensus that the dual-isotope scan that uses both thallium-201 and Tc-99m is not recommended.[30][6]

Dosing for MPI: In all MPI protocols, the American Society of Nuclear Cardiology recommends 2.5 to 3.5 mCi of thallium-201 for the initial dose (stress or rest imaging), while for the reinjections, if required in the protocol, an additional dose of 1 to 2 mCi of thallium-201 is recommended.[30] The 2020 Brazilian guideline advocates avoiding the use of doses higher than 3.5 mCi to reduce radiation exposure.[6] In all cases, the dosage must be adjusted according to the patient's body mass index.[33][34][30] In a study, Bednarova et al. proposed using ultra-low-dose thallium-201 (0.014mCi/kg body weight) with CZT (cadmium-zinc-telluride) SPECT technology for MPI, which seems promising.[31]

Dosing for olfacto-scintigraphy: 0.3 ml solution of thallium-201 (22MBq) is administered nasally into the olfactory clefts, and 24 hours later, uptake of thallium-201 is evaluated with SPECT Scan. This test may correlate with CT, MRI, and T & T olfactometry findings for further analysis.[25][24][23]

Adverse Effects

Possible reported adverse effects of Thallium-201, when used for scintigraphy, include severe allergic reactions and gastrointestinal disturbances.[24][25] Mustafa Yildirim et al. have demonstrated possible genetic damages with thallium-201 scans for myocardial perfusion imaging.[35] A study done to assess the effects of radiopharmaceuticals on testicular function showed a higher probability of ill-defined adverse effects with thallium-201 compared to Tc-99m.[36] Besides these adverse effects, there are some limitations to thallium-201 scans.

Tc-based radiopharmaceuticals have largely replaced thallium-201 in myocardial perfusion imaging studies because of its longer half-life of 73 hrs (compared to Tc of 6 hrs) and its low-energy emission, which consequently needs a greater radiation dose but yields images of inferior quality than Tc scans.[37][31] There have been no adverse effects reported with thallium-201 olfacto-scintigraphy.[38][23][39]

Monitoring

The usual dose of thallium-201 used for SPECT scans is small; thus, it is safe for use.[2] However, some considerations are necessary for certain populations. The recommendation is that lactating mothers should discontinue breastfeeding after a thallium-201 scan because it is excreted in breast milk. The exact time for discontinuation is still debatable, but a period of 2 weeks has been suggested by a study as the optimum period.

Different studies have shown that the mother can pump breast milk before the procedure and freeze it for storage. After the scan, she can pump the breast milk and either throw it away or freeze it for about 30 days before use. Another option is to measure the radioactivity level of breast milk before commencing breastfeeding again to ensure safety.[40] A study done to assess the maternal-fetal transfer of thallium-201 in rats showed significant retention in organs of the mother as well as the fetus.[41]

Toxicity

At a significantly higher dose than that used in routine imaging, thallium-201 can potentially cause hair loss, gastrointestinal hemorrhage, and neurological symptoms. Death reportedly results at concentrations of about 2.8mg/kg.[29] The FDA has approved the use of Prussian Blue for the therapeutic removal of thallium-201.[42] Lansoprazole has also been shown to be useful for this process, as demonstrated by studies done in mice and rabbits.[43]

Enhancing Healthcare Team Outcomes

Thallium-201 administration for scintigraphy requires an interprofessional team of healthcare professionals involving clinicians in different fields, nurses, laboratory technicians, and specialized nuclear pharmacists. These various disciplines must coordinate their activities and engage in open communication regarding the patient's case to achieve the best diagnostic results and prevent any possible adverse events. [Level 5]

Patients undergoing MPI should be advised to fast for a minimum of 4 hours before the scan.[1] It is advisable for patients undergoing nuclear myocardial scans with dipyridamole or adenosine to avoid caffeine for at least 24 hours.[44] Administration of thallium-201 must occur through a venous line abiding by the local radiation protocols.[45] 

Any article over the thorax that might have the potential to attenuate the image requires removal. Before initiating the scan, detailed cardiopulmonary history and examination are necessary.[1] Qualified health professional supervision is a requirement during the stress test. Equipment and drugs needed for cardiac life support must be present within reach of the certified professional at all times. The patient's condition during the procedure must be monitored continuously with EKG and vitals measurement. The handling of all the necessary equipment, radiopharmaceutical agents, and waste must follow standard protocols and guidelines from the respective authorities and the state.[1] [Level 5]

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

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Disclosure: Bhavya Poudyal declares no relevant financial relationships with ineligible companies.

Disclosure: Pallabi Shrestha declares no relevant financial relationships with ineligible companies.

Disclosure: Yuvraj Chowdhury declares no relevant financial relationships with ineligible companies.