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Impact of Cell-Proliferation-Associated Gene Expression on 2-Deoxy-2-[18F]fluoro-d-Glucose (FDG) Kinetics as Measured by Dynamic Positron Emission Tomography (dPET) in Colorectal Tumors

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Abstract

Introduction

Glucose transporters and hexokinases determine the kinetics of 2-deoxy-2-[18F]fluoro-d-glucose (FDG). However, the genes controlling these proteins are not independent and may be modulated from other biological processes, e.g., like angiogenesis and proliferation. The impact of cell-proliferation-related genes on the FDG kinetics was assessed in colorectal tumors in this study.

Methods

Patients with primary colorectal tumors (n = 25) were examined with positron emission tomography and FDG within 2 days prior to surgery. Tissue specimens were obtained from the colorectal tumor and the normal colon by surgery and gene expression was assessed using gene arrays.

Results

Overall, an increase of the expression of proliferation associated genes was observed by a factor of 2–5.3 for the colorectal tumors as compared with the normal colon. Correlation analysis revealed an impact of cdk2 on K1, thus directing to a modulation of the FDG uptake into the cells. The correlations were generally higher for the FDG influx as compared with the standardized uptake value (SUV). The influx was mainly correlated with proliferation inhibiting genes (cyclin G2, cdk inhibitor 1 C, cdk inhibitor 2B). It was possible to predict the expression of cyclin D2 using a multiple linear regression function and the parameters of the FDG kinetics with r = 0.67. Using a group based analysis it was possible to demonstrate, that tumors with an SUV >12 are associated with a high expression of cyclin D2 in the colorectal tumors. If the gene expression data for cyclin D1, cyclin G2, cdk2, cdk6 and cdk inhibtor 2B were used, the overall FDG uptake as measured by the SUV could be predicted with r = 0.75.

Conclusions

The results suggest that the FDG kinetics is modulated by proliferation associated genes. Especially K1, the parameter for the FDG transport into the cells, is modulated by cdk2. Tumors with a SUV exceeding 12 have usually a higher expression of cyclin D2. The parameters of the FDG kinetics can be used to predict the expression of proliferation associated genes individually.

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References

  1. Strauss LG, Conti PS (1991) The applications of PET in clinical oncology. J Nucl Med 32:623–648

    PubMed  CAS  Google Scholar 

  2. Higashi K, Clavo AC, Wahl RL (1993) Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. J Nucl Med 34:414–419

    PubMed  CAS  Google Scholar 

  3. Tateishi U, Yamaguchi U, Seki K, Terauchi T, Arai Y, Hasegawa T (2006) Glut-1 expression and enhanced metabolism are associated with tumour grade in bone and soft tissue sarcomas: a prospective evaluation by [18F]fluorodeoxyglucose positron emission tomography. Eur J Nucl Med Mol Imaging 33:683–691

    Article  PubMed  CAS  Google Scholar 

  4. Vesselle H, Schmidt RA, Pugsley JM et al (2000) Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 6:3837–3844

    PubMed  CAS  Google Scholar 

  5. Pugachev A, Ruan S, Carlin S et al (2005) Dependence of FDG uptake on tumour microenvironment. Int J Radiat Oncol Biol Phys 62:545–553

    Article  PubMed  CAS  Google Scholar 

  6. Strauss LG, Klippel S, Pan L, Schönleben K, Haberkorn U, Dimitrakopoulou-Strauss A (2007) Assessment of quantitative FDG PET data in primary colorectal tumours: which parameters are important with respect to tumour detection? Eur J Nucl Med Mol Imaging 34:868–877

    Article  PubMed  Google Scholar 

  7. Burt BM, Humm JL, Kooby DA et al (2001) Using positron emission tomography with [18 F]FDG to predict tumour behavior in experimental colorectal cancer. Neopasia 3:189–195

    Article  CAS  Google Scholar 

  8. Dimitrakopoulou-Strauss A, Strauss LG, Schwarzbach M et al (2001) Dynamic PET 18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading. J Nucl Med 42:713–720

    PubMed  CAS  Google Scholar 

  9. Strauss LG, Dimitrakopoulou-Strauss A, Koczan D et al (2004) 18F-FDG kinetics and gene expression in giant cell tumours. J Nucl Med 45:1528–1535

    PubMed  CAS  Google Scholar 

  10. Strauss LG, Koczan D, Klippel S et al (2008) Impact of angiogenesis-related gene expression on the tracer kinetics of 18F-FDG kinetics in colorectal tumours. J Nucl Med 49:1238–1244

    Article  PubMed  CAS  Google Scholar 

  11. Ohtake T, Kosaka N, Watanabe T, Yokoyama I, Moritan T, Masuo M et al (1991) Noninvasive method to obtain input function for measuring glucose utilization of thoracic and abdominal organs. J Nucl Med 32:1432–1438

    PubMed  CAS  Google Scholar 

  12. Pan L, Mikolajczyk K, Strauss LG, Haberkorn U, Dimitrakopoulou-Strauss A (2007) Machine learning based parameter imaging and kinetic modeling of PET data [abstract]. J Nucl Med 48(suppl):158P

    Google Scholar 

  13. Dimitrakopoulou-Strauss A, Strauss LG, Mikolajczyk K, Burger C, Lehnert T, Bernd LG, Ewerbeck V (2003) On the fractal nature of dynamic positron emission tomography (PET) studies world. J Nucl Med 2:306–313

    Google Scholar 

  14. Strauss LG, Pan L, Koczan D et al (2007) Fusion of positron emission tomography (PET) and gene array data: a new approach for the correlative analysis of molecular biological and clinical data. IEEE Trans Med Imag 26:804–812

    Article  Google Scholar 

  15. Wunder JS, Paulian G, Huyos AG, Heller G, Meyers PA, Healey JH (1998) The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma. J Bone Joint Surg Am 80:1020–1033

    Article  PubMed  CAS  Google Scholar 

  16. Zhang J, Kang SK, Wang L, Touijer A, Hricak H (2009) Distribution of renal tumour growth rates determined by using serial volumetric CT measurements. Radiology 250:137–144

    Article  PubMed  Google Scholar 

  17. Goh V, Halligan S, Daley F, Wellsted DM, Guenther T, Bartram CT (2008) Colorectal tumour vascularity: quantitative assessment with multidetector CT—do tumour perfusion measurements reflect angiogenesis? Radiology 249:910–917

    Article  Google Scholar 

  18. Schiepers C, Chen W, Dahlbom M, Cloughesy T, Hoh CK, Huang SC (2007) 18F-fluorothymidine kinetics of malignant brain tumours. Eur J Nucl Med Mol Imaging 34:1003–1111

    Article  PubMed  CAS  Google Scholar 

  19. Dimitrakopoulou-Strauss A, Strauss LG (2008) The role of 18 F-FLT in cancer imaging: does it really reflect proliferation? Eur J Nucl Med Mol Imaging 35:523–526

    Article  PubMed  Google Scholar 

  20. Riedl CC, Akhurst T, Larson S et al (2007) 18F-FDG PET scanning correlates with tissue markers of poor prognosis and predicts mortality for patients after liver resection for colorectal metastases. J Nucl Med 48:771–775

    Article  PubMed  Google Scholar 

  21. Buck AK, Halter G, Schirrmeister H et al (2003) Imaging proliferation in lung tumours with PET: 18F-FLT versus 18F-FDG. J Nucl Med 44:1426–1431

    PubMed  CAS  Google Scholar 

  22. Henriksson E, Kjellén E, Baldetorp B et al (2009) Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck. J Exp Clin Cancer Res 28:17. doi:10.1186/1756-9966-28-17

    Article  PubMed  Google Scholar 

  23. Sánchez Salmóna A, Garridoa M, Abdulkaderb I, Gudec F, Leónd L, Ruibala A (2009) The immunohistochemical expression of cyclin B1 is associated with higher maxSUV in 18F-FDG-PET in non-small cell lung cancer patients. Initial results. Rev Esp Med Nucl 28:63–65

    Article  Google Scholar 

  24. Zhou YL, Deng CS (2005) Correlations of expressions of Glut1 and HIF-1alpha to cellular proliferation of colorectal adenocarcinoma. Ai Zheng 24:685–689

    PubMed  CAS  Google Scholar 

  25. Sakamaki T, Casimiro MC, Ju X et al (2006) Cyclin D1 determines mitochondrial function in vivo. Mol Cell Biol 26:5449–5469

    Article  PubMed  CAS  Google Scholar 

  26. Lee SH, Heo JS, Han HJ (2007) Effect of hypoxia on 2-deoxyglucose uptake and cell cycle regulatory protein expression of mouse embryonic stem cells: involvement of Ca2+/PKC, MAPKs and HIF-1alpha. Cell Physiol Biochem 19:269–282

    Article  PubMed  CAS  Google Scholar 

  27. Strauss LG, Dimitrakopoulou-Strauss A, Haberkorn U (2003) Shortened PET data acquisition protocol for the quantification of 18F-FDG kinetics. J Nucl Med 44:1933–1939

    PubMed  CAS  Google Scholar 

  28. Strauss LG, Pan L, Cheng C, Haberkorn U, Dimitrakopoulou-Strauss A (2009) Accuracy of shortened acquisition protocols for the quantitative assessment of the 2-tissue compartment method using dynamic PET F-18-deoxyglucose (FDG) studies. [abstract]. J Nucl Med 50(2):630

    Google Scholar 

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Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Ludwig G. Strauss, Leyun Pan, Caixia Cheng, Uwe Haberkorn & Antonia Dimitrakopoulou-Strauss

  2. Institute of Immunology, University Rostock, Rostock, Germany

    Dirk Koczan

  3. Surgical Clinic A, Klinikum Ludwigshafen, Ludwigshafen, Germany

    Sven Klippel & Stefan Willis

  4. Department of Nuclear Medicine, Ruprecht-Karls-University, Heidelberg, Germany

    Uwe Haberkorn

Authors
  1. Ludwig G. Strauss
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  2. Dirk Koczan
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  3. Sven Klippel
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  8. Antonia Dimitrakopoulou-Strauss
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Correspondence to Ludwig G. Strauss.

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Strauss, L.G., Koczan, D., Klippel, S. et al. Impact of Cell-Proliferation-Associated Gene Expression on 2-Deoxy-2-[18F]fluoro-d-Glucose (FDG) Kinetics as Measured by Dynamic Positron Emission Tomography (dPET) in Colorectal Tumors. Mol Imaging Biol 13, 1290–1300 (2011). https://doi.org/10.1007/s11307-010-0465-z

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  • DOI: https://doi.org/10.1007/s11307-010-0465-z

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