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Application of ex vivo micro-computed tomography for assessment of in vivo fluorescence and plain radiographic imaging for monitoring bone metastases and osteolytic lesions

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Abstract

The intracardiac injection model is a commonly used in vivo model to test therapeutic response in bone metastases. However, few studies have critically compared the performance of different imaging methods in terms of sensitivity and quantitative assessment of osteolytic lesions. We performed in vivo optical and plain radiographic imaging of bone metastases followed by high-sensitivity ex vivo micro-computed tomography (micro-CT) imaging. This approach allowed for quantitative assessment of in vivo imaging techniques using fluorescence and plain radiography. Comparison of lesions detected in vivo by fluorescent optical imaging with ex vivo micro-CT revealed that the limited spatial resolution of fluorescent optical imaging may underestimate the number of bone metastases. Radiography was compared with micro-CT for the detection of osteolytic lesions. When using dichotomous yes/no grading, there was a 64% agreement in detection of osteolytic lesions. When subjective semiquantitative grading methods were used to assess the extent of osteolytic lesions, a positive association between the micro-CT grades and the square root of the radiography-based grades was observed (p < 0.05). Micro-CT also showed a significant association with fluorescent optical values; however, no such association was observed between lesion scores based on radiographs and those based on fluorescent imaging. The findings reveal an approximate two-fold sensitivity for micro-CT compared to plain radiography in the detection of osteolytic lesions. Significant associations between micro-CT-based osteolytic lesion grade and tumor growth characterized by increased fluorescent area document the value of these two techniques for the assessment of osteolytic bone metastases.

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References

  1. Papagelopoulos PJ, Savvidou OD, Galanis EC, Mavrogenis AF, Jacofsky DJ, Frassica FJ, Sim FH (2006) Advances and challenges in diagnosis and management of skeletal metastases. Orthopedics 29:609–620 quiz 621-602

    PubMed  Google Scholar 

  2. Tai P, Yu E, Vinh-Hung V, Cserni G, Vlastos G (2004) Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries. BMC Cancer 4:60

    Article  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96

    Article  PubMed  Google Scholar 

  4. Mundy G (2001) Preclinical models of bone metastases. Semin Oncol 28:2–8

    Article  PubMed  CAS  Google Scholar 

  5. Phadke PA, Mercer RR, Harms JF, Jia Y, Frost AR, Jewell JL, Bussard KM, Nelson S, Moore C, Kappes JC et al (2006) Kinetics of metastatic breast cancer cell trafficking in bone. Clin Cancer Res 12:1431–1440

    Article  PubMed  Google Scholar 

  6. Rosol TJ, Tannehill-Gregg SH, LeRoy BE, Mandl S, Contag CH (2003) Animal models of bone metastasis. Cancer 97:748–757

    Article  PubMed  Google Scholar 

  7. Kaijzel EL, van der Pluijm G, Lowik CW (2007) Whole-body optical imaging in animal models to assess cancer development and progression. Clin Cancer Res 13:3490–3497

    Article  PubMed  Google Scholar 

  8. Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452:580–589

    Article  PubMed  CAS  Google Scholar 

  9. Peyruchaud O, Winding B, Pecheur I, Serre CM, Delmas P, Clezardin P (2001) Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions. J Bone Miner Res 16:2027–2034

    Article  PubMed  CAS  Google Scholar 

  10. Wetterwald A, van der Pluijm G, Que I, Sijmons B, Buijs J, Karperien M, Lowik CW, Gautschi E, Thalmann GN, Cecchini MG (2002) Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. Am J Pathol 160:1143–1153

    Article  PubMed  Google Scholar 

  11. Ito M (2011) Recent progress in bone imaging for osteoporosis research. J Bone Miner Metab 29:131–140

    Article  PubMed  Google Scholar 

  12. Jacobsson H, Goransson H (1991) Radiological detection of bone and bone marrow metastases. Med Oncol Tumor Pharmacother 8:253–260

    PubMed  CAS  Google Scholar 

  13. Arrington SA, Schoonmaker JE, Damron TA, Mann KA, Allen MJ (2006) Temporal changes in bone mass and mechanical properties in a murine model of tumor osteolysis. Bone 38:359–367

    Article  PubMed  CAS  Google Scholar 

  14. Fritz V, Louis-Plence P, Apparailly F, Noel D, Voide R, Pillon A, Nicolas JC, Muller R, Jorgensen C (2007) Micro-CT combined with bioluminescence imaging: a dynamic approach to detect early tumor-bone interaction in a tumor osteolysis murine model. Bone 40:1032–1040

    Article  PubMed  CAS  Google Scholar 

  15. Mouchess ML, Sohara Y, Nelson MD Jr, De CYA, Moats RA (2006) Multimodal imaging analysis of tumor progression and bone resorption in a murine cancer model. J Comput Assist Tomogr 30:525–534

    Article  PubMed  Google Scholar 

  16. Postnov AA, Rozemuller H, Verwey V, Lokhorst H, De Clerck N, Martens AC (2009) Correlation of high-resolution X-ray micro-computed tomography with bioluminescence imaging of multiple myeloma growth in a xenograft mouse model. Calcif Tissue Int 85:434–443

    Article  PubMed  CAS  Google Scholar 

  17. Li Z, Schem C, Shi YH, Medina D, Zhang M (2008) Increased COX2 expression enhances tumor-induced osteoclastic lesions in breast cancer bone metastasis. Clin Exp Metastasis 25:389–400

    Article  PubMed  Google Scholar 

  18. Gillies RJ, Bhujwalla ZM, Evelhoch J, Garwood M, Neeman M, Robinson SP, Sotak CH, Van Der Sanden B (2000) Applications of magnetic resonance in model systems: tumor biology and physiology. Neoplasia 2:139–151

    Article  PubMed  CAS  Google Scholar 

  19. Brasch R, Pham C, Shames D, Roberts T, van Dijke K, van Bruggen N, Mann J, Ostrowitzki S, Melnyk O (1997) Assessing tumor angiogenesis using macromolecular MR imaging contrast media. J Magn Reson Imaging 7:68–74

    Article  PubMed  CAS  Google Scholar 

  20. Taylor JS, Tofts PS, Port R, Evelhoch JL, Knopp M, Reddick WE, Runge VM, Mayr N (1999) MR imaging of tumor microcirculation: promise for the new millennium. J Magn Reson Imaging 10:903–907

    Article  PubMed  CAS  Google Scholar 

  21. Bauerle T, Merz M, Komljenovic D, Zwick S, Semmler W (2010) Drug-induced vessel remodeling in bone metastases as assessed by dynamic contrast enhanced magnetic resonance imaging and vessel size imaging: a longitudinal in vivo study. Clin Cancer Res Off J Am Assoc Cancer Res 16:3215–3225

    Article  Google Scholar 

  22. Acton PD, Zhou R (2005) Imaging reporter genes for cell tracking with PET and SPECT. Q J Nucl Med Mol Imaging 49:349–360

    PubMed  CAS  Google Scholar 

  23. Gambhir SS (2002) Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2:683–693

    Article  PubMed  CAS  Google Scholar 

  24. Jenkins DE, Hornig YS, Oei Y, Dusich J, Purchio T (2005) Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice. Breast Cancer Res 7:R444–R454

    Article  PubMed  CAS  Google Scholar 

  25. Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD, Doubrovin M, Ponomarev V, Gerald WL, Blasberg R, Massague J (2005) Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115:44–55

    PubMed  CAS  Google Scholar 

  26. Winnard PT Jr, Kluth JB, Raman V (2006) Noninvasive optical tracking of red fluorescent protein-expressing cancer cells in a model of metastatic breast cancer. Neoplasia 8:796–806

    Article  PubMed  CAS  Google Scholar 

  27. Choy G, O’Connor S, Diehn FE, Costouros N, Alexander HR, Choyke P, Libutti SK (2003) Comparison of noninvasive fluorescent and bioluminescent small animal optical imaging. Biotechniques 35:1028–1030

    Google Scholar 

  28. Glüer CC, Schem C, Tiwari S, Heller M, Jonat W (2009) Molekulare Bildgebung in der gynäkologischen Onkologie. Der Gynäkologe 42:859–864

    Article  Google Scholar 

  29. Kaijzel EL, Snoeks TJ, Buijs JT, van der Pluijm G, Lowik CW (2009) Multimodal imaging and treatment of bone metastasis. Clin Exp Metastasis 26:371–379

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The breast cancer cell line was provided by Prof. Dr. Toshiyuki Yoneda (University of Texas Health Science Center). We are grateful for the technical assistance from Gabi Trompke, Sigrid Hamann and Frank Rösel. This work was supported by research grants from the state of Schleswig–Holstein (projects MOIN-SH and MOIN CC) and by an unrestricted research grant from Pfizer Inc.

Conflict of interest

All authors have no conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Medical Physics, Department of Diagnostic Radiology, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany

    Sanjay Tiwari, Christian Graeff, Jaime Peña & Claus-C Glüer

  2. Division of Molecular Oncology, Institute for Experimental Cancer Research, Comprehensive Cancer Center North, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany

    Holger Kalthoff

  3. Department of Gynecology, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany

    Christian Schem, Ann-Christin Lorenzen & Walter Jonat

  4. Department of Diagnostic Radiology, University Hospital Schleswig–Holstein, Campus Kiel, Kiel, Germany

    Ole Kayser, Claas Wiese & Martin Heller

  5. Institute for Osteology and Biomechanics, University Hospital Eppendorf, Hamburg, Germany

    Robert P. Marshall

  6. Division of Medical Physics, Department of Diagnostic Radiology, University Hospital Schleswig–Holstein, Am Botanischen Garten 14, 24118, Kiel, Germany

    Sanjay Tiwari

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  1. Sanjay Tiwari
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  2. Christian Schem
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Correspondence to Sanjay Tiwari.

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Tiwari, S., Schem, C., Lorenzen, AC. et al. Application of ex vivo micro-computed tomography for assessment of in vivo fluorescence and plain radiographic imaging for monitoring bone metastases and osteolytic lesions. J Bone Miner Metab 30, 373–380 (2012). https://doi.org/10.1007/s00774-011-0335-z

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  • DOI: https://doi.org/10.1007/s00774-011-0335-z

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