Annals of Nuclear Medicine

, Volume 22, Issue 10, pp 833–839

Usefulness of triple-phase thallium-201 SPECT in non-small-cell lung cancer (NSCLC): association with proliferative activity

  • Seigo Fujita
  • Shigeki Nagamachi
  • Hideyuki Wakamatsu
  • Ryuichi Nishii
  • Shigemi Futami
  • Shozo Tamura
  • Yasunori Matsuzaki
  • Toshio Onizuka
  • Kinta Hatakeyama
  • Yujiro Asada
Original Article



The conventional delayed scan in dual phase of thallium-201 (201Tl) single-photon emission computed tomography (SPECT) is useful for estimating the viability of non-small-cell lung cancer (NSCLC). However, the influence of tumor blood flow cannot be ignored by the scan at 4 h after the tracer injection. For the purpose of improving the diagnostic capability and for clarifying the association between 201Tl uptake and proliferative activity, we investigated the usefulness of super-delayed scan obtained at 24 h in triple-phase 201Tl SPECT.


A total of 122 patients with lung nodule, 106 of NSCLC and 16 of benign nodule, were given 201Tl SPECT before the tumor resection. Early image (15 min), delayed image (4 h), and super-delayed image (24 h) were obtained after intravenous injection of 201Tl chloride (111 MBq). On the each SPECT image, regions of interest (ROIs) were placed over the tumor contour (T) and contra-lateral normal lung tissue (N) area on one transverse view clearly defined lesions, and T/N ratio on the early image (ER), the delayed image (DR), and the super-delayed image (sDR), and retention indexes (RI and sRI) were calculated. All patients underwent subsequent surgical excision, and the specimens were immunostained for Ki-67 and CD34. The proliferative capability was measured as a percentage of positive nuclear area for Ki-67 (MIB-1 index). The angiogenesis was measured density of positive micro-vessels for CD34 (micro-vessel density, MVD). Correlation analysis was performed to evaluate the relationship between the MIB-1 index, MVD, and SPECT parameters.


The diagnostic accuracy of sDR in the differential of NSCLC was higher than that of DR (83.6% vs. 91.8%). Both DR and sDR were positively correlated with MIB-1 index. The correlation coefficient was higher in sDR (0.53 vs. 0.69). The MIB-1 index of the increasing pattern (RI < sRI) group was significantly higher (P < 0.001) than that of the decreasing pattern (RI > sRI) group.


The super-delayed scan in the triple-phase 201Tl SPECT is more useful than conventional delayed scan for both the diagnostic capability and assessing proliferation of NSCLC.


Triple-phase 201Tl SPECT Super-delayed image Proliferation NSCLC 


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  1. 1.
    Bernard JP, Louie O, Altorki N. Staging and the surgical management of lung cancer. Radiol Clin North Am 2000;38:545–561.CrossRefGoogle Scholar
  2. 2.
    Cox PH, Belfer AJ, Pompe WB. Thallium-201 chloride uptake in tumors: a possible complication in heart scintigraphy. Br J Radiol 1976;16:425–430.Google Scholar
  3. 3.
    Salvatore M, Carratu L, Porta E. Thallium-201 as a positive indicator for lung neoplasm: preliminary experiments. Radiology 1976;121:487–488.PubMedGoogle Scholar
  4. 4.
    Tonami N, Hisada K. Clinical experience of tumor imaging with Tl-201 chloride. Clin Nucl Med 1977;2:75–81.CrossRefGoogle Scholar
  5. 5.
    Tonami N, Shuke N, Yokoyama K, Seki H, Takayama T, Kinuya S, et al. Tl-201 single photon emission computed tomography in the evaluation of suspected lung cancer. J Nucl Med 1989;30:997–1004.PubMedGoogle Scholar
  6. 6.
    Flores LG II, Ochiai E, Nagamachi S, Jinnouchi S, Ohnishi T, Futami S, et al. The diagnostic role of 201Tl SPECT imaging in patients with lung tumor: comparison with computed tomography. Nucl Med Commun 1996;17:493–499.PubMedCrossRefGoogle Scholar
  7. 7.
    Nagamachi S, Jinnnouchi S, Nishii R, Futami S, Tamura S, Matsuzaki Y, et al. Reevaluation of 201Tl-SPECT for patients with solitary pulmonary nodule: comparison study with biopsy method and tumor marker measurement. Kaku Igaku 2001;38:737–745.PubMedGoogle Scholar
  8. 8.
    Fujita S, Nagamachi S, Nishi R, Futami S, Nakada H, Kuroki M, et al. Usefulness of 201Tl SPECT in the predication of mediastinal lymph nodes metastasis in patients with non small cell lung cancer (NSCLC). Kaku Igaku 2004;1:1–7.Google Scholar
  9. 9.
    Fujita S, Nagamachi S, Nishi R, Wakamatsu H, Futami S, Tamura S, et al. Relationship between cancer cell proliferation, tumor angiogenesis and thallium-201 uptake in nonsmall cell lung cancer (NSCLC). Nucl Med Commun. 8:989–997.Google Scholar
  10. 10.
    Watanabe K. Thallium scintigraphy. Houshasei douigennso kennsa gijutsu. 5th ed. Tokyo: Nanzanndo; 2000. p. 449–451.Google Scholar
  11. 11.
    Tonami N. Thallium scintigraphy: a new textbook of clinical nuclear medicine. 3rd ed. Tokyo: Kanehara; 1999. p. 527–538.Google Scholar
  12. 12.
    Takekawa H, Itoh K, Abe S, Ogura S, Isobe H, Sukou N, et al. Retention index of thallium-201 single photon emission computerized tomography (SPECT) as an indicator of metastasis in adenocarcinoma of the lung. Br J cancer 1994;70:315–318.PubMedGoogle Scholar
  13. 13.
    Sehweil AM, Mckillop JH, Milroy R, Wilson R, Abdel-Dayem HM, Omar YT. Mechanism of 201Tl uptake in tumors. Eur J Nucl Med 1989;15:376–379.PubMedCrossRefGoogle Scholar
  14. 14.
    Ishibashi M, Fujii T, Yamana H, Fujimoto K, Rikimaru T, Hayashi A, et al. Relationship between cancer cell proliferation and thallium-201 uptake in lung cancer. Ann Nucl Med 2000;14:255–261.PubMedCrossRefGoogle Scholar
  15. 15.
    Takekawa H, Itoh K, Abe S, Ogura S, Isobe H, Furudate M, et al. Thallium-201 uptake, histopathological differentiation and Na-K ATPase in lung adenocarcinoma. J Nucl Med 1996;37:955–958.PubMedGoogle Scholar
  16. 16.
    Fukumoto M. Single-photon agents for tumor imaging: 201Tl, 99mTc-MIBI, and 99mTc-tetrofosmin. Ann Nucl Med 2004;18:79–95.PubMedCrossRefGoogle Scholar
  17. 17.
    Yu YH, Hsu WH, Hsu NY, Lin TY, Hsia TC, Sun SS, et al. The usefulness of dual phase 201Tl SPECT for differentiating pulmonary malignancies from benign lesions. Jpn J Clin Oncol 2004;34:445–451.PubMedCrossRefGoogle Scholar
  18. 18.
    Ueda T, Kaji Y, Wakisaka S, Watanabe K, Hoshi H, Jinnouchi S, et al. Time sequential single photon emission computed tomography studies in brain tumor using thallium-201. Eur J Nucl Med 1993;20:138–145.PubMedCrossRefGoogle Scholar
  19. 19.
    Tominaga M, Sueoka N, Irie K, Iwanaga K, Tokunaga O, Hayashi S, et al. Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67. Lung Cancer 2003;40:45–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Mascaux C, Martin B, Verdebout JM, Meert AP, Ninane V, Sculier JP. Fragile histidine triad protein expression in nonsmall cell lung cancer and correlation with Ki-67 and with p53. Eur Respir J 2003;21:753–758.PubMedCrossRefGoogle Scholar
  21. 21.
    Haga Y, Hiroshima K, Iyoda A, Shibuya K, Shimamura F, Iizasa T, et al. Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer. Ann Thorac Surg 2003;75:1727–1732.PubMedCrossRefGoogle Scholar
  22. 22.
    Takahashi S, Kamata Y, Tamo W, Koyanagi M, Hatanaka R, Yamada Y, et al. Relationship between postoperative and expression of cyclin E, p27, and Ki-67 in non-small cell lung cancer without lymph node metastases. Int J Clin Oncol 2002;7:349–355.PubMedCrossRefGoogle Scholar
  23. 23.
    Carbogman P, Tincani G, Crafa P, Sansebastiano G, Pazzini L, Zoni R, et al. Biological markers in non-small cell lung cancer: retrospective study of 10 year follow-up after surgery. J Cardiovasc Surg 2002;43:545–548.Google Scholar
  24. 24.
    Poleri C, Morero JL, Nieva B, Vazquez MF, Rodriguez C, de Titto E, et al. Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: histopathologic and immunohistochemical analysis. Chest 2003;123:1858–1867.PubMedCrossRefGoogle Scholar
  25. 25.
    Yamazaki K, Abe S, Takekawa H, Sukoh N, Watanabe N, Ogura S, et al. Tumor angiogenesis in human lung adenocarcinoma. Cancer 1994;74:2245–2250.PubMedCrossRefGoogle Scholar
  26. 26.
    Yano T, Tanikawa S, Fujie T, Masutani M, Horie T. Vascular endothelial growth factor expression and neovascularisation in non-small cell lung cancer. Eur J Cancer 2000;36:601–609.PubMedCrossRefGoogle Scholar
  27. 27.
    Gupta NC, Maloof J, Gunel E. Probability of malignancy in solitary pulmonary nodule using fluorine-18-FDG and PET. J Nucl Med 1996;37:943–948.PubMedGoogle Scholar
  28. 28.
    Lewis P, Griffin S, Marsden P, Gee T, Nunan T, Malsey M, et al. Whole-body 18F-fluorodeoxyglucose positron emission tomography in preoperative evaluation of lung cancer. Lancet 1994;344:1265–1266.PubMedCrossRefGoogle Scholar
  29. 29.
    Oriuchi N. Diagnosis of Lung cancer with FDG-PET. Japan J Diagn Imaging 2003;23:1142–1150.Google Scholar
  30. 30.
    Duhaylongsod FG, Lowe VJ, Patz EF Jr, Vaughn AL, Coleman RE, Wolfe WG. Detection of primary and recurrent lung cancer by means of F-18 fluorodeoxyglucose positron emission tomography (FDG PET). J Thorac Cardiovasc Surg 1995;110:130–139.PubMedCrossRefGoogle Scholar
  31. 31.
    Higashi K, Ueda Y, Yagishita M, Arisaka Y, Sakurai A, Oguchi M, et al. FDG PET measurement of the proliferative potential of non-small cell lung cancer. J Nucl Med 2000;41:85–92.PubMedGoogle Scholar
  32. 32.
    Ahuja V, Coleman RE, Herndon J, Patz EF Jr. The prognostic significance of fluorodeoxyglucose positron emission tomography imaging for patients with non-small cell lung cancer. Cancer 1998;83:918–924.PubMedCrossRefGoogle Scholar
  33. 33.
    Pauwels EK, Ribeiro MJ, Stoot JH, McCready VR, Bourguignon M, Maziere B, et al. FDG accumulation and tumor biology. Nucl Med Biol 1998;25:317–322.PubMedCrossRefGoogle Scholar
  34. 34.
    Lardinois D, Brack T, Gaspert A, Spahr T, Schneiter D, Steinert HC, et al. Staging of non-small cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003;48:2500–2507.CrossRefGoogle Scholar
  35. 35.
    Kawakami Y, Suga K, Yamashita T, Iwanaga H, Zaki M, Matsunaga N. Initial application of respiratory-gated 201Tl SPECT in pulmonary malignant tumors. Nucl Med Commun 2005;26:303–313PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2008

Authors and Affiliations

  • Seigo Fujita
    • 1
  • Shigeki Nagamachi
    • 1
  • Hideyuki Wakamatsu
    • 1
  • Ryuichi Nishii
    • 1
  • Shigemi Futami
    • 1
  • Shozo Tamura
    • 1
  • Yasunori Matsuzaki
    • 2
  • Toshio Onizuka
    • 2
  • Kinta Hatakeyama
    • 3
  • Yujiro Asada
    • 3
  1. 1.Department of RadiologyMiyazaki Medical CollegeMiyazakiJapan
  2. 2.Department of the Second SurgeryMiyazaki Medical CollegeMiyazakiJapan
  3. 3.Department of the First PathologyMiyazaki Medical CollegeMiyazakiJapan

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