Is Tc99m-MIBI scintigraphy a predictor of response to pre-operative neoadjuvant chemotherapy in Osteosarcoma?

Document Type : Original Article

Authors

1 Department of Orthopedic surgery, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

2 Nuclear Medicine Research Center, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pathology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Oncology, Omid Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Multidrug resistance (MDR), which may be due to the over expression of P-glycoprotein (Pgp) and/or MRP, is a major problem in neoadjuvant chemotherapy of osteosarcoma. The aim of this study was to investigate the role of Tc-99m MIBI scan for predicting the response to pre-operative chemotherapy.
Methods: Twenty-five patients (12 males and 13 females, aged between 8 and 52y) with osteosarcoma were studied. Before the chemotherapy, planar 99mTc-MIBI anterior and posterior images were obtained 10-min [tumor-to-background ratio: (T1/B1)10min] and 3-hr after tracer injection. After completion of chemotherapy, again 99mTc-MIBI scan was performed at 10-min after tracer injection. In addition to calculation of decay corrected tumor to background (T/B) ratios ,  using the 10-min and 3-hr images of the pre-chemotherapy scintigraphy , percent wash-out rate (WR%) of 99mTc-MIBI was calculated. Using the 10-min images of the pre- and post-chemotherapy scans, the percent reduction in uptake at the tumor site after treatment (Red%) was also calculated. Then after surgical resection, tumor response was assessed by percentage of necrosis.
Results: All patients showed significant 99mTc-MIBI uptake in early images. Only 9 patients showed good response to chemotherapy (necrosis≥90%) while 16 patients were considered as non-responder (necrosis<90%). There was no statistical significant difference between non-responders and responders in (T1/B1)10min.There was a significant negative correlation between WR% and percentage of necrosis (P=0.001). On the other hand, there was a significant correlation between Red% and percentage of necrosis (P<0.001).There was also statistical significant difference in WR% and Red% between non-responders and responders (both P< 0.001).
Conclusion: Washout rate of 99mTc-MIBI in pre-chemotherapy scintigraphy as well as Red% using pre- and post-chemotherapy MIBI scintigraphy are useful methods for predicting response to neoadjuvant chemotherapy.      

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References

  1. Burak Z, Moretti JL, Ersoy O, Sanli U, Kantar M, Tamgac F, et al. 99mTc-MIBIimaging as a predictor of therapy response in osteosarcoma compared with multidrug resistance-associated protein and P-glycoprotein expression. J Nucl Med 2003;44(9):1394-401.
  2. Gomes CM, Welling M, Que I, Henriquez NV, van der Pluijm G, Romeo S, et al. Functional imaging of multidrug resistance in an orthotopic model of osteosarcoma using 99mTc-sestamibi. Eur J Nucl Med Mol Imaging 2007;34(11):1793-803.
  3. Taki J, Sumiya H, Asada N, Ueda Y, Tsuchiya H, Tonami N. Assessment of P-Glycoprotein in Patients with Malignant Bone and Soft-Tissue Tumors Using Technetium- 99m-MIB I Scintigraphy. J Nucl Med 1998;39(7):1179-84.
  4. Yapar Z, Kibar M, Yapar AF, Uguz A, Ozbarlas S, Gonlusen G. The value of Tc-99m-tetrofosmin scintigraphy in the assessment of P-glycoprotein in patients with malignant bone and soft-tissue tumors. Ann Nucl Med 2003;17(6):443-9.
  5. Baldini N, Scotlandi K, Serra M, Picci P, Bacci G, Sottili S, et al. P-glycoprotein expression in osteosarcoma: a basis for risk-adapted adjuvant chemotherapy. J Orthop Res 1999; 17(5): 629-32.
  6. Kusuzaki K, Hirata M, Takeshita H, Murata H, Hashiguchi S, Ashihara T, et al. Relationship between P-glycoprotein positivity, doxorubicin binding ability and histologic response to preoperative chemotherapy in osteosarcoma. Cancer Lett 1999; 138(1-2): 203-8.
  7. Fallahi B, Saghari M, Fard Esfahani A, Eftekhari M, Iravani M, Beiki D, et al. The value of 99mTc-MIBI whole body scintigraphy in active and in remission multiple myeloma. Hell J Nucl Med 2005;8(3):165-8.
  8. Vergote J, Moretti JL, de Vries EG, Garnier-Suillerot A. Comparison of the kinetics of active efflux of 99mTc-MIBIin cells with p-glycoprotein mediated and multidrug resistance protein- associated multidrug resistance phenotypes. Eur J Biochem 1998; 252(1):140-6.
  9. Burak Z, Ersoy O, Moretti JL, Erinç R, Ozcan Z, Dirlik A, et al. The role of 99mTc-MIBIscintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response. Eur J Nucl Med 2001;28(9):1341-50.
  10. Ballinger JR, Hua HA, Berry BW, Firby P, Boxen I. 99mTc sestamibi as an agent for imaging P-glycoprotein-mediated multidrug resistance: in vitro and in vivo studies in a rat breast tumor cell line and in vivo doxorubicin-resistant variant. Nucl Med Commun 1995; 16(4):253-7.
  11. Kapucu LO, Akyüz C, Vural G, Oguz A, Atasever T, Büyükpamukçu M, et al. Evaluation of therapy response in children with untreated malignant lymphomas using technetium-99m sestamibi. J Nucl Med 1997; 38(2):243-7.
  12. Sasaki M, Kuwabara Y, Ichiya Y, Yoshida T, Nakagawa M, Soeda H, et al. Prediction of the chemosensitivity of lung cancer by 99mTc hexakis-2-methoxyisobutyl isonitrile SPECT. J Nucl Med 1999; 40(11):1778–83.
  13. Moretti JL, Azaloux H, Boisseron D, Kouyoumdjian JC, Vilcoq J. Primary breast cancer imaging with technetium-99m sestamibi and its relation with P-glycoprotein overexpression. Eur J Nucl Med 1996; 23(8):980-6.
  14. Serra M, Scotlandi K, Manara MC, Maurici D, Benini S, Sarti M, et al. Analysis of P-glycoprotein expression in osteosarcoma. Eur J Cancer 1995;31A(12):1998–2002.
  15. Baldini N, Scotlandi K, Barbandi-Brodano G, Manara MC, Maurici D, Bacci G, et al. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med 1995;333(21):1380-5.
  16. Moretti JL, Cordobes MD, Starzec A, de Beco V, Vergote J, Benazzouz F, et al. Involvement of glutathione in loss of technetium-99m MIBI accumulation related to membrane MDR protein expression in tumor cells. J Nucl Med 1998; 39(7):1214–8.
  17. Luker G, Fracasso PM, Dobkin J, Piwnica-Worms D. Modulation of the multidrug resistance P-glycoprotein: detection with technetium-99m sestamibi in vivo. J Nucl Med 1997; 38(3):369-72.
  18. Del Vecchio S, Ciarmiello A, Pace L, Potena MI, Carriero MV, Mainolfi C, et al. Fractional retention of technetium-99m sestamibi as an index of P-glycoprotein expression in untreated breast cancer patients. J Nucl Med 1997; 38(9):1348–51.
  19. Sohaib M, Wiqar MA, Ali MK, Hussain F, Umer-i-Farooq. A single 99mTc-MIBI study to predict response to neoadjuvant treatment in sarcoma patiens. Hell J Nucl Med 2011;14(2):140-5.
  20. Trieb K, Kotz R. Proteins expressed in osteosarcoma and serum levels as prognostic factors. Int J Biochem Cell Biol 2001;33(1):11–7.
  21. Wunder JS, Bull SB, Aneliunas V, Lee PD, Davis AM, Beauchamp CP, et al. MDR1 gene expression and outcome in osteosarcoma: a prospective, multicenter study. J Clin Oncol 2000;18(14):2685-94.
  22. Uozaki H, Horiuchi H, Ishida T, Iijima T, Imamura T, Machinami R. Overexpression of resistance-related proteins (metallothio-neins, glutathione-S-transferase pi, heat shock protein 27 and lung resistance-related protein) in osteosarcoma: relationship with poor prognosis. Cancer 1997;79(12): 2336-44.
  23. Moretti JL, Hauet N, Caglar M, Rebillard O, Burak To use MIBI or not to use MIBI? That is the question when assessing tumour cells. Eur J Nucl Med Mol Imaging 2005;32(7):836-42.
Asia Oceania Journal of Nuclear Medicine and Biology
Volume 1, Issue 2 - Serial Number 2
October 2013
Pages 22-27

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