Journal of Neuro-Oncology

, Volume 89, Issue 2, pp 225–230 | Cite as

99mTc-Tetrofosmin brain SPECT in the assessment of meningiomas—correlation with histological grade and proliferation index

  • Andreas D. Fotopoulos
  • George A. Alexiou
  • Ann Goussia
  • Athanasios Papadopoulos
  • Athanasios P. Kyritsis
  • Konstantinos S. Polyzoidis
  • Spyridon Voulgaris
  • Spyridon Tsiouris
Clinical-patient studies


Meningiomas account for about 30% of all intracranial tumors. Evaluation of their proliferation rate is useful for assessing their biological behavior. We evaluated prospectively whether 99mTc-Tetrofosmin (99mTc-TF) uptake in meningiomas correlates with cellular proliferative activity and with tumor grade. We prospectively studied 18 meningioma cases. Brain single-photon emission computed tomography (SPECT) by 99mTc-TF was performed within a week prior to surgical excision. In the excised tumor specimens we assessed Ki-67 antigen expression. 14 of 18 patients had benign meningiomas, while the remaining four had anaplastic meningiomas. A significant correlation was found between both 99mTc-TF uptake and tumor grade (r = 0.722, P = 0.001) and between 99mTc-TF uptake and Ki-67 expression (r = 0.930, P < 0.001). There was a significant correlation between the intensity of tracer uptake and tumor recurrence at 1 year postoperative (r = 0.574, P = 0.02). This pilot study implies that 99mTc-TF brain SPECT could prove useful in differentiating benign from anaplastic meningiomas and is a potential indicator of their proliferative activity.


Meningioma 99mTc-Tetrofosmin Cell proliferation Ki-67 MIB-1 


  1. 1.
    Nakasu S, Hirano A, Shimura T et al (1987) Incidental meningiomas at autopsy study. Surg Neurol 27:319–322PubMedCrossRefGoogle Scholar
  2. 2.
    Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMedCrossRefGoogle Scholar
  3. 3.
    Kayaselcuk F, Zorludemir S, Bal N et al (2004) The expression of survivin and Ki-67 in meningiomas: correlation with grade and clinical outcome. J Neurooncol 67:209–214PubMedCrossRefGoogle Scholar
  4. 4.
    Raghavan D, Brecher ML, Johnson DH et al (1999) Textbook of uncommon cancer. Wiley, New YorkGoogle Scholar
  5. 5.
    Onda K, Davis RL, Shibuya M et al (1994) Correlation between the bromodeoxyuridine labeling index and the MIB-1 and Ki-67 proliferating cell indices in cerebral gliomas. Cancer 74:1921–1926PubMedCrossRefGoogle Scholar
  6. 6.
    Jaros E, Perry RH, Adam L et al (1992) Prognostic implications of p53 protein, epidermal growth factor receptor and Ki-67 labelling in brain tumours. Br J Cancer 66:373–385PubMedGoogle Scholar
  7. 7.
    Chen W, Cloughesy T, Kamdar N et al (2005) Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG. J Nucl Med 46:945–952PubMedGoogle Scholar
  8. 8.
    Nagashima G, Aoyagi M, Wakimoto H et al (1995) Immunohistochemical detection of progesterone receptors and the correlation with Ki-67 labeling indices in paraffin-embedded sections of meningiomas. Neurosurgery 37:478–482PubMedCrossRefGoogle Scholar
  9. 9.
    Ohta M, Iwaki T, Kitamoto T et al (1994) MIB1 staining index and scoring of histologic features in meningioma. Cancer 74:3176–3189PubMedCrossRefGoogle Scholar
  10. 10.
    Amatya VJ, Takeshima Y, Sugiyama K et al (2001) Immunohistochemical study of Ki-67(MIB-1), p53 protein, p21 WAF1, and p21KIP1 expression in benign, atypical and anaplastic meningiomas. Hum Pathol 32:970–975PubMedCrossRefGoogle Scholar
  11. 11.
    Ho DM, Hsu CY, Ting LT et al (2002) Histopathology and MIB-1 labeling index predicted recurrence of meningiomas: a proposal of diagnostic criteria for patients with atypical meningioma. Cancer 94:1538–1547PubMedCrossRefGoogle Scholar
  12. 12.
    Nakaguchi H, Fujimaki T, Matsuno A et al (1999) Postoperative residual tumor growth of meningioma can be predicted by MIB-1 immunohistochemistry. Cancer 85:2249–2254PubMedCrossRefGoogle Scholar
  13. 13.
    Kasuya H, Kubo O, Tanaka M et al (2006) Clinical and radiological features related to the growth potential of meningioma. Neurosurg Rev 29:293–296PubMedCrossRefGoogle Scholar
  14. 14.
    Smith TA (1998) FDG uptake, tumour characteristics and response to therapy: a review. Nucl Med Commun 19:97–105PubMedCrossRefGoogle Scholar
  15. 15.
    Papantoniou VJ, Souvatzoglou MA, Valotassiou V et al (2004) Relationship of cell proliferation (Ki-67) to 99mTc-(V)DMSA uptake in breast cancer. Breast Cancer Res. 6:R56-R62.
  16. 16.
    Denoyer D, Perek N, Le Jeune N et al (2005) Correlation between 99mTc-(V)-DMSA uptake and constitutive level of phosphorylated focal adhesion kinase in an in vitro model of cancer cell lines. Eur J Nucl Med Mol Imaging 32:820–827PubMedCrossRefGoogle Scholar
  17. 17.
    Soricelli A, Cuocolo A, Varrone A et al (1998) Technetium-99m-tetrofosmin uptake in brain tumors by SPECT: comparison with thallium-201 imaging. J Nucl Med 39:802–805PubMedGoogle Scholar
  18. 18.
    Choi JY, Kim SE, Shin HJ et al (2000) Brain tumor imaging with 99mTc-tetrofosmin: comparison with 201Tl, 99mTc-MIBI, and 18F-fluorodeoxyglucose. J Neurooncol 46:63–70PubMedCrossRefGoogle Scholar
  19. 19.
    Simpson D (1957) The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22–39PubMedGoogle Scholar
  20. 20.
    Hsu D, Efird J, Hedley Whyte E (1997) Progesterone and estrogen receptors in meningiomas, prognostic considerations. J Neurosurg 86:113–120PubMedGoogle Scholar
  21. 21.
    Tyagi A, Chakrabarty A, Franks A (2004) MIB1 proliferation index in meningiomas: does it predict recurrence? A clinicopathological study. Br J Neurosurg 18:357–361PubMedCrossRefGoogle Scholar
  22. 22.
    Shibuya M, Hoshino T, Ito S et al (1992) Meningiomas: clinical implications of a high proliferative potential determined by Bromodeoxyuridine labelling. Neurosurgery 30:494–498PubMedCrossRefGoogle Scholar
  23. 23.
    Wakimoto H, Aoyagi M, Nakayama T et al (1996) Prognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas. Cancer 77:373–380PubMedCrossRefGoogle Scholar
  24. 24.
    Quiňones-Hinojosa A, Sanai N, Smith JS et al (2005) Techniques to assess the proliferative potential of brain tumors. J Neurooncol 74:19–30PubMedCrossRefGoogle Scholar
  25. 25.
    Stemmer-Rachamimov AO, Louis DN (1997) Histopathologic and immunohistochemical prognostic factors in malignant gliomas. Curr Opin Oncol 9:230–234PubMedGoogle Scholar
  26. 26.
    Di X, Nishizaki T, Harada K, Kajiwara K et al (1997) Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1. J Exp Clin Cancer Res 16:153–157PubMedGoogle Scholar
  27. 27.
    Oriuchi N, Tamura M, Shibazaki T et al (1993) Clinical evaluation of thallium-201 SPECT in supratentorial gliomas:relationship to histologic grade, prognosis and proliferative activities. J Nucl Med 34:2085–2089PubMedGoogle Scholar
  28. 28.
    Prayson R (2005) The Utility of MIB-1/Ki-67 immunostaining in the evaluation of central nervous system neoplasms. Adv Anat Pathol 12:144–148PubMedCrossRefGoogle Scholar
  29. 29.
    Roser F, Samii M, Ostertag H et al (2004) The Ki-67 proliferation antigen in meningiomas. Experience in 600 cases. Acta Neurochir (Wien) 146:37–44CrossRefGoogle Scholar
  30. 30.
    Matsuno A, Fujimaki T, Sasaki T et al (1996) Clinical and histopathological analysis of proliferative potentials of recurrent and non-recurrent meningiomas. Acta Neuropathol 91:504–510PubMedCrossRefGoogle Scholar
  31. 31.
    Kakinuma K, Tanaka R, Onda K (1998) Proliferative potential of recurrent meningiomas as evaluated by labeling indices of BudR and Ki-67, tumour doubling time. Acta Neurochir (Wien) 140:26–32CrossRefGoogle Scholar
  32. 32.
    Sasaki K, Matsumura K, Tsuji T et al (1988) Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors. Cancer 62:989–993PubMedCrossRefGoogle Scholar
  33. 33.
    Lippitz B, Cremerius U, Mayfrank L et al (1996) PET-study of intracranial meningiomas: correlation with histopathology, cellularity and proliferation rate. Acta Neurochir Suppl 65:108–111PubMedGoogle Scholar
  34. 34.
    Iuchi T, Iwadate Y, Namba H et al (1992) Glucose and methionine uptake and proliferative activity in meningiomas. Neurol Res 21:640–644Google Scholar
  35. 35.
    Gungor F, Bezircioglu H, Guvenc G et al (2000) Correlation of thallium-201 uptake with proliferating cell nuclear antigen in brain tumours. Nucl Med Commun 21:803–810PubMedCrossRefGoogle Scholar
  36. 36.
    Tedeschi E, Soricelli A, Brunetti A et al (1996) Different thallium-201 single-photon emission tomographic patterns in benign and aggressive meningiomas. Eur J Nucl Med 23:1478–1484PubMedCrossRefGoogle Scholar
  37. 37.
    Jinnouchi S, Hoshi H, Ohnishi T et al (1993) Thallium-201 SPECT for predicting histological types of meningiomas. J Nucl Med 34:2091–2094PubMedGoogle Scholar
  38. 38.
    Platts EA, North TL, Pickett RD et al (1995) Mechanism of uptake of technetium–tetrofosmin. I. Uptake into isolated adult rat ventricular myocytes and subcellular localization. J Nucl Cardiol 2:317–326PubMedCrossRefGoogle Scholar
  39. 39.
    Spanu A, Ginesu F, Pirina P et al (2003) The usefulness of 99mTc-tetrofosmin SPECT in the detection of intrathoracic malignant lesions. Int J Oncol 22:639–649PubMedGoogle Scholar
  40. 40.
    Karayalcin U, Ciftci F, Boz A et al (1997) The value of Tc-99 m tetrofosmin thyroid scintigraphy in patients with nodular goiter. Ann Nucl Med 11:285–290PubMedCrossRefGoogle Scholar
  41. 41.
    Schillaci O, Danieli R, Romano P et al (2005) Scintimammography for the detection of breast cancer. Expert Rev Med Devices 2:191–196PubMedCrossRefGoogle Scholar
  42. 42.
    Perek N, Prevot N, Koumanov F et al (2000) Involvement of the glutathione S-conjugate compounds and the MRP protein in Tc-99m-tetrofosmin and Tc-99m-sestamibi uptake in glioma cell lines. Nucl Med Biol 27:299–307PubMedCrossRefGoogle Scholar
  43. 43.
    Le Jeune N, Perek N, Denoyer D et al (2005) Study of monoglutathionyl conjugates TC-99 M-sestamibi and TC-99 M tetrofosmin transport mediated by the multidrug resistance-associated protein isoform 1 in glioma cells. Cancer Biot Radiopharm 20:249–259CrossRefGoogle Scholar
  44. 44.
    Le Jeune N, Perek N, Denoyer D et al (2004) Influence of glutathione depletion on plasma membrane cholesterol esterification and on Tc-99 m-sestamibi and Tc-99 m-Tetrofosmin uptakes: a comparative study in sensitive U-87-MG and multidrug resistance MRP1 human glioma cells. Cancer Biother Radiopharm 19:411–421PubMedGoogle Scholar
  45. 45.
    Alexiou GA, Fotopoulos AD, Papadopoulos A et al (2007) Evaluation of brain tumor recurrence by 99 mTc-Tetrofosmin SPECT: A prospective pilot study. Ann Nucl Med 21:293–298PubMedCrossRefGoogle Scholar
  46. 46.
    Alexiou GA, Tsiouris S, Kyritsis AP et al (2007) The use of PET scan in glioblastoma multiforme. J Neurooncol 86:359–360PubMedCrossRefGoogle Scholar
  47. 47.
    Alexiou GA, Bokharhii JA, Kyritsis AP et al (2006) Tc-99m Tetrofosmin SPECT for the differentiation of a cerebellar hemorrhage mimicking a brain metastasis from a renal cell carcinoma. J Neurooncol 78:207–208PubMedCrossRefGoogle Scholar
  48. 48.
    Alexiou GA, Tsiouris S, Goussia A et al (2008) Evaluation of glioma proliferation by 99mTc-Tetrofosmin. Neuro Oncol 10:104–105PubMedCrossRefGoogle Scholar
  49. 49.
    Coons SW, Johnson PC (1993) Regional heter.ogeneity in the proliferative activity of human gliomas as measured by the Ki-67 labeling index. J Neuropathol Exp Neurol 52:609–618PubMedCrossRefGoogle Scholar
  50. 50.
    Dalrymple S, Parisi JE, Roche PC et al (1993) Changes in proliferating cell nuclear antigen expression in glioblastoma multiforme cells along a stereotactic biopsy trajectory. Neurosurgery 35:1036–1045CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Andreas D. Fotopoulos
    • 1
  • George A. Alexiou
    • 2
  • Ann Goussia
    • 3
  • Athanasios Papadopoulos
    • 1
  • Athanasios P. Kyritsis
    • 4
  • Konstantinos S. Polyzoidis
    • 2
  • Spyridon Voulgaris
    • 2
  • Spyridon Tsiouris
    • 1
  1. 1.Department of Nuclear MedicineUniversity of Ioannina School of MedicineIoanninaGreece
  2. 2.Department of NeurosurgeryUniversity of Ioannina School of MedicineIoanninaGreece
  3. 3.Department of PathologyUniversity of Ioannina School of MedicineIoanninaGreece
  4. 4.Department of NeurologyUniversity of Ioannina School of MedicineIoanninaGreece

Personalised recommendations