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:
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 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 the 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 in the diagnosis of 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 for the diagnosis of 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 the diagnosis of 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 post 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]
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, which makes 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 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 us to assess the perfusion while the delayed images help us to evaluate the viability of the myocardium.[32]
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 on the fact 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. propose the use of 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 findings of CT, MRI, and T & T olfactometry for further analysis. [25][24][23]
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 that of 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]
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 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]
At a significantly higher dose than 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 shown to be useful for this process, as demonstrated by studies done in mice and rabbits.[43]
Thallium-201 administration for scintigraphy requires an interprofessional team of healthcare professionals involving physicians in different fields, nurses, laboratory technicians, and pharmacists. 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. 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]
[1] | Strauss HW,Miller DD,Wittry MD,Cerqueira MD,Garcia EV,Iskandrian AS,Schelbert HR,Wackers FJ,Balon HR,Lang O,Machac J, Procedure guideline for myocardial perfusion imaging 3.3. Journal of nuclear medicine technology. 2008 Sep; [PubMed PMID: 18703619] |
[2] | McKillop JH, Thallium 201 scintigraphy. The Western journal of medicine. 1980 Jul; [PubMed PMID: 7222645] |
[3] | Brindis RG,Douglas PS,Hendel RC,Peterson ED,Wolk MJ,Allen JM,Patel MR,Raskin IE,Hendel RC,Bateman TM,Cerqueira MD,Gibbons RJ,Gillam LD,Gillespie JA,Hendel RC,Iskandrian AE,Jerome SD,Krumholz HM,Messer JV,Spertus JA,Stowers SA, ACCF/ASNC appropriateness criteria for single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI): a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group and the American Society of Nuclear Cardiology endorsed by the American Heart Association. Journal of the American College of Cardiology. 2005 Oct 18; [PubMed PMID: 16226194] |
[4] | Fathala A, Myocardial perfusion scintigraphy: techniques, interpretation, indications and reporting. Annals of Saudi medicine. 2011 Nov-Dec; [PubMed PMID: 22048510] |
[5] | Malhotra S,Gomez J,Doukky R, Assessment of myocardial viability using single-photon emission computed tomography myocardial perfusion imaging. Current opinion in cardiology. 2019 Sep; [PubMed PMID: 31219878] |
[6] | Mastrocola LE,Amorim BJ,Vitola JV,Brandão SCS,Grossman GB,Lima RSL,Lopes RW,Chalela WA,Carreira LCTF,Araújo JRN,Mesquita CT,Meneghetti JC, Update of the Brazilian Guideline on Nuclear Cardiology - 2020. Arquivos brasileiros de cardiologia. 2020 Feb; [PubMed PMID: 32215507] |
[7] | Kailasnath P,Sinusas AJ, Technetium-99m-labeled myocardial perfusion agents: Are they better than thallium-201? Cardiology in review. 2001 May-Jun; [PubMed PMID: 11304401] |
[8] | Beller GA,Holzgrefe HH,Watson DD, Effects of dipyridamole-induced vasodilation on myocardial uptake and clearance kinetics of thallium-201. Circulation. 1983 Dec; [PubMed PMID: 6640881] |
[9] | Giordano A,Marozzi P,Meduri G,Ficola U,Calcagni ML,Vaccaro A,Rubini G,Attard M,Li Puma M,Ricci R,Corsello S, Quantitative comparison of technetium-99m tetrofosmin and thallium-201 images of the thyroid and abnormal parathyroid glands. European journal of nuclear medicine. 1999 Aug; [PubMed PMID: 10436206] |
[10] | MacFarlane SD,Hanelin LG,Taft DA,Ryan JA Jr,Fredlund PN, Localization of abnormal parathyroid glands using thallium-201. American journal of surgery. 1984 Jul; [PubMed PMID: 6742331] |
[11] | Chou FF,Wang PW,Sheen-Chen SM, Preoperative localisation of parathyroid glands in primary hyperparathyroidism. The European journal of surgery = Acta chirurgica. 1997 Dec; [PubMed PMID: 9449440] |
[12] | Bhansali A,Masoodi SR,Bhadada S,Mittal BR,Behra A,Singh P, Ultrasonography in detection of single and multiple abnormal parathyroid glands in primary hyperparathyroidism: comparison with radionuclide scintigraphy and surgery. Clinical endocrinology. 2006 Sep; [PubMed PMID: 16918953] |
[13] | Wakamatsu H,Noguchi S,Yamashita H,Yamashita H,Tamura S,Jinnouchi S,Nagamachi S,Futami S, Technetium-99m tetrofosmin for parathyroid scintigraphy: a direct comparison with (99m)Tc-MIBI, (201)Tl, MRI and US. European journal of nuclear medicine. 2001 Dec; [PubMed PMID: 11734921] |
[14] | Sekiyama K,Akakura K,Mikami K,Mizoguchi K,Tobe T,Nakano K,Numata T,Konno A,Ito H, Usefulness of diagnostic imaging in primary hyperparathyroidism. International journal of urology : official journal of the Japanese Urological Association. 2003 Jan; [PubMed PMID: 12534918] |
[15] | Hussain FS,Hussain NS, Clinical Utility of Thallium-201 Single Photon Emission Computed Tomography and Cerebrospinal Fluid Epstein-Barr Virus Detection Using Polymerase Chain Reaction in the Diagnosis of AIDS-Related Primary Central Nervous System Lymphoma. Cureus. 2016 May 10; [PubMed PMID: 27330874] |
[16] | Antinori A,De Rossi G,Ammassari A,Cingolani A,Murri R,Di Giuda D,De Luca A,Pierconti F,Tartaglione T,Scerrati M,Larocca LM,Ortona L, Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1999 Feb; [PubMed PMID: 10080599] |
[17] | Giancola ML,Rizzi EB,Schiavo R,Lorenzini P,Schininà V,Alba L,Del Grosso B,Gigli B,Rosati S,Mango L,Bibbolino C,Antinori A, Reduced value of thallium-201 single-photon emission computed tomography in the management of HIV-related focal brain lesions in the era of highly active antiretroviral therapy. AIDS research and human retroviruses. 2004 Jun; [PubMed PMID: 15242533] |
[18] | Nguyen P,Knapp-Wachsner A,Hsieh CG,Kamangar N, Pulmonary Kaposi Sarcoma without Mucocutaneous Involvement: The Role of Sequential Thallium and Gallium Scintigraphy. Journal of clinical imaging science. 2019; [PubMed PMID: 31448163] |
[19] | Lee VW,Fuller JD,O'Brien MJ,Parker DR,Cooley TP,Liebman HA, Pulmonary Kaposi sarcoma in patients with AIDS: scintigraphic diagnosis with sequential thallium and gallium scanning. Radiology. 1991 Aug; [PubMed PMID: 2068302] |
[20] | Kubo T,Shimose S,Fujimori J,Furuta T,Ochi M, Quantitative (201)thallium scintigraphy for prediction of histological response to neoadjuvant chemotherapy in osteosarcoma; systematic review and meta-analysis. Surgical oncology. 2015 Sep; [PubMed PMID: 26092710] |
[21] | Maria BL,Drane WE,Mastin ST,Jimenez LA, Comparative value of thallium and glucose SPECT imaging in childhood brain tumors. Pediatric neurology. 1998 Nov; [PubMed PMID: 9880139] |
[22] | Howman-Giles R,Uren RF,Shaw PJ, Thallium-201 scintigraphy in pediatric soft-tissue tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1995 Aug; [PubMed PMID: 7629580] |
[23] | Shiga H,Taki J,Yamada M,Washiyama K,Amano R,Matsuura Y,Matsui O,Tatsutomi S,Yagi S,Tsuchida A,Yoshizaki T,Furukawa M,Kinuya S,Miwa T, Evaluation of the olfactory nerve transport function by SPECT-MRI fusion image with nasal thallium-201 administration. Molecular imaging and biology. 2011 Dec; [PubMed PMID: 21136183] |
[24] | Shiga H,Okuda K,Taki J,Watanabe N,Tonami H,Kinuya S,Miwa T, Nasal thallium-201 uptake in patients with parosmia with and without hyposmia after upper respiratory tract infection. International forum of allergy [PubMed PMID: 31356735] |
[25] | Shiga H,Taki J,Washiyama K,Yamamoto J,Kinase S,Okuda K,Kinuya S,Watanabe N,Tonami H,Koshida K,Amano R,Furukawa M,Miwa T, Assessment of olfactory nerve by SPECT-MRI image with nasal thallium-201 administration in patients with olfactory impairments in comparison to healthy volunteers. PloS one. 2013; [PubMed PMID: 23469046] |
[26] | Kinoshita Y,Shiga H,Washiyama K,Ogawa D,Amano R,Ito M,Tsukatani T,Furukawa M,Miwa T, Thallium transport and the evaluation of olfactory nerve connectivity between the nasal cavity and olfactory bulb. Chemical senses. 2008 Jan; [PubMed PMID: 17905744] |
[27] | Iida Y,Kasagi K,Misaki T,Arai K,Tokuda Y,Konishi J, Visualization of suppressed normal thyroid tissue by thallium-201 in patients with toxic nodular goiter. Clinical nuclear medicine. 1988 Apr; [PubMed PMID: 3370895] |
[28] | Erdil TY,Onsel C,Kanmaz B,Caner B,Sönmezoğlu K,Ciftçi I,Turoğlu T,Kabasakal L,Sayman HB,Uslu I, Comparison of 99mTc-methoxyisobutyl isonitrile and 201T1 scintigraphy in visualization of suppressed thyroid tissue. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2000 Jul; [PubMed PMID: 10914905] |
[29] | Bradley-Moore PR,Lebowitz E,Greene MW,Atkins HL,Ansari AN, Thallium-201 for medical use. II: Biologic behavior. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1975 Feb; [PubMed PMID: 1110422] |
[30] | Henzlova MJ,Duvall WL,Einstein AJ,Travin MI,Verberne HJ, ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2016 Jun; [PubMed PMID: 26914678] |
[31] | Bednárová V,Kincl V,Kamínek M,Vašina J,Panovský R,Máchal J, The prognostic value of ultra low-dose thallium myocardial perfusion protocol using CZT SPECT. The international journal of cardiovascular imaging. 2019 Jun; [PubMed PMID: 30680654] |
[32] | Sharir T,Slomka P, Dual-isotope myocardial perfusion SPECT imaging: Past, present, and future. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2018 Dec; [PubMed PMID: 28664393] |
[33] | Ishihara M,Taniguchi Y,Onoguchi M,Shibutani T, Optimal thallium-201 dose in cadmium-zinc-telluride SPECT myocardial perfusion imaging. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2018 Jun; [PubMed PMID: 28008559] |
[34] | 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] |
[35] | Yildirim M,Ikbal M,Tos T,Seven B,Pirim I,Varoglu E, Genotoxicity of thallium-201 in patients with angina pectoris undergoing myocardial perfusion study. The Tohoku journal of experimental medicine. 2005 Aug; [PubMed PMID: 15997200] |
[36] | Manetou A,Limouris GS, Effects in the testes after SPECT myocardial perfusion with Tl-201 or Tc-99m hexaMIBI. Anticancer research. 1997 May-Jun; [PubMed PMID: 9179242] |
[37] | Won KS,Song BI, Recent trends in nuclear cardiology practice. Chonnam medical journal. 2013 Aug; [PubMed PMID: 24010067] |
[38] | Shiga H,Taki J,Okuda K,Watanabe N,Tonami H,Nakagawa H,Kinuya S,Miwa T, Prognostic value of olfactory nerve damage measured with thallium-based olfactory imaging in patients with idiopathic olfactory dysfunction. Scientific reports. 2017 Jun 15; [PubMed PMID: 28620194] |
[39] | Washiyama K,Shiga H,Hirota K,Tsuchida A,Yamamoto J,Yagi S,Yoshizaki T,Furukawa M,Amano R,Miwa T, Biological safety of nasal thallium-201 administration: a preclinical study for olfacto-scintigraphy. Journal of radiation research. 2011; [PubMed PMID: 21905306] |
[40] | Thallous Chloride Tl 201 2006; [PubMed PMID: 29999756] |
[41] | Rade JE,Marafante E,Sabbioni E,Gregotti C,Di Nucci A,Manzo L, Placental transfer and retention of 201Ti-thallium in the rat. Toxicology letters. 1982 May; [PubMed PMID: 7101321] |
[42] | Sandal N,Mittal G,Bhatnagar A,Pathak DP,Singh AK, Preparation, Characterization, and {i}In Vivo{/i} Pharmacoscintigraphy Evaluation of an Intestinal Release Delivery System of Prussian Blue for Decorporation of Cesium and Thallium. Journal of drug delivery. 2017; [PubMed PMID: 29318045] |
[43] | Nishad DK,Rawat HS,Singh T,Bhatnagar A,Mittal G, Decorporation potential of lansoprazole against radiothallium ({sup}201{/sup}Tl) in internally contaminated BALB/c mice and New Zealand White rabbits. Human [PubMed PMID: 29909643] |
[44] | Powles KE,Hessian RC,Ruddy TD, Practicing safe SPECT: caffeine abstinence in nuclear myocardial perfusion imaging. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2008 Sep-Oct; [PubMed PMID: 18761274] |
[45] | Anagnostopoulos C,Harbinson M,Kelion A,Kundley K,Loong CY,Notghi A,Reyes E,Tindale W,Underwood SR, Procedure guidelines for radionuclide myocardial perfusion imaging. Heart (British Cardiac Society). 2004 Jan; [PubMed PMID: 14676223] |