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Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

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Abstract

Purpose

We evaluated whether the dynamic profile of L-11C-methionine (11C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET).

Methods

Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic 11C-MET PET was performed by small animal PET up to 120 min after injection of 11C-MET. The next day, after overnight fasting, the rats were injected with 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG), and dynamic 18F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated.

Results

11C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of 11C-MET uptake in the granuloma was significantly different from that in the tumor (p < 0.001). In the static analysis of 11C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 ± 0.09) was significantly lower than that in the tumor (1.72 ± 0.18, p < 0.01). The dynamic patterns, static images, and mean SUVs of 18F-FDG in the granuloma were similar to those in the tumor (p = NS).

Conclusion

Dynamic 11C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings.

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References

  1. Brudin LH, Valind S, Rhodes CG, Pantin CF, Sweatman M, Jones T, et al. Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography. Eur J Nucl Med 1994;21:297–305.

    Article  PubMed  CAS  Google Scholar 

  2. Lewis PJ, Salama A. Uptake of fluorine-18-fluorodeoxyglucose in sarcoidosis. J Nucl Med 1994;35:1647–9.

    PubMed  CAS  Google Scholar 

  3. Ohtsuka T, Nomori H, Watanabe K, Naruke T, Orikasa H, Yamazaki K, et al. False-positive findings on [18F]FDG-PET caused by non-neoplastic cellular elements after neoadjuvant chemoradiotherapy for non-small cell lung cancer. Jpn J Clin Oncol 2005;35:271–3.

    Article  PubMed  Google Scholar 

  4. Lorenzen J, de Wit M, Buchert R, Igel B, Bohuslavizki KH. Granulation tissue: pitfall in therapy control with F-18-FDG PET after chemotherapy. Nuklearmedizin 1999;38:333–6.

    PubMed  CAS  Google Scholar 

  5. Conessa C, Hervé S, Foehrenbach H, Poncet JL. FDG-PET scan in local follow-up of irradiated head and neck squamous cell carcinomas. Ann Otol Rhinol Laryngol 2004;113:628–35.

    PubMed  Google Scholar 

  6. van Waarde A, Cobben DC, Suurmeijer AJ, Maas B, Vaalburg W, de Vries EF, et al. Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model. J Nucl Med 2004;45:695–700.

    PubMed  Google Scholar 

  7. van Waarde A, Jager PL, Ishiwata K, Dierckx RA, Elsinga PH. Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation. J Nucl Med 2006;47:150–4.

    PubMed  Google Scholar 

  8. Jacobs AH, Dittmar C, Winkeler A, Garlip G, Heiss WD. Molecular imaging of gliomas. Mol Imaging 2002;1:309–35.

    Article  PubMed  CAS  Google Scholar 

  9. Kubota K, Kubota R, Yamada S, Tada M. Effects of radiotherapy on the cellular uptake of carbon-14 labeled L-methionine in tumor tissue. Nucl Med Biol 1995;22:193–8.

    Article  PubMed  CAS  Google Scholar 

  10. Kubota R, Kubota K, Yamada S, Tada M, Takahashi T, Iwata R, et al. Methionine uptake by tumor tissue: a microautoradiographic comparison with FDG. J Nucl Med 1995;36:484–92.

    PubMed  CAS  Google Scholar 

  11. Reinhardt MJ, Kubota K, Yamada S, Iwata R, Yaegashi H. Assessment of cancer recurrence in residual tumors after fractionated radiotherapy: a comparison of fluorodeoxyglucose, L-methionine and thymidine. J Nucl Med 1997;38:280–7.

    PubMed  CAS  Google Scholar 

  12. Chung JK, Kim YK, Kim SK, Lee YK, Paek S, Yeo JS, et al. Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET. Eur J Nucl Med Mol Imaging 2002;29:176–82.

    Article  PubMed  CAS  Google Scholar 

  13. Moulin-Romsée G, D’Hondt E, de Groot T, Goffin J, Sciot R, Mortelmans L, et al. Non-invasive grading of brain tumours using dynamic amino acid PET imaging: does it work for 11C-methionine? Eur J Nucl Med Mol Imaging 2007;34:2082–7.

    Article  PubMed  Google Scholar 

  14. Zhang H, Yoshikawa K, Tamura K, Tomemori T, Sagou K, Tian M, et al. [(11)C]Methionine positron emission tomography and survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy. Clin Cancer Res 2004;10:1764–72.

    Article  PubMed  CAS  Google Scholar 

  15. Kanegae K, Nakano I, Kimura K, Kaji H, Kuge Y, Shiga T, et al. Comparison of MET-PET and FDG-PET for differentiation between benign lesions and lung cancer in pneumoconiosis. Ann Nucl Med 2007;21:331–7.

    Article  PubMed  Google Scholar 

  16. Tsuyuguchi N, Sunada I, Iwai Y, Yamanaka K, Tanaka K, Takami T, et al. Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery: is a differential diagnosis possible? J Neurosurg 2003;98:1056–64.

    Article  PubMed  Google Scholar 

  17. Yamada Y, Uchida Y, Tatsumi K, Yamaguchi T, Kimura H, Kitahara H, et al. Fluorine-18-fluorodeoxyglucose and carbon-11-methionine evaluation of lymphadenopathy in sarcoidosis. J Nucl Med 1998;39:1160–6.

    PubMed  CAS  Google Scholar 

  18. Zhao S, Kuge Y, Kohanawa M, Takahashi T, Kawashima H, Temma T, et al. Extensive FDG uptake and its modification with corticosteroid in a granuloma rat model: an experimental study for differentiating granuloma from tumors. Eur J Nucl Med Mol Imaging 2007;34:2096–105.

    Article  PubMed  CAS  Google Scholar 

  19. Zhao S, Kuge Y, Yi M, Kohanawa M, Zhao Y, Kanegae K, et al. Dynamics of 18F-FDG uptake in experimental granulomas induced with activated macrophages: comparison with malignant tumors [abstract]. J Nucl Med 2008;49(Suppl 1):318P.

    Google Scholar 

  20. Zhao S, Kuge Y, Kohanawa M, Takahashi T, Zhao Y, Yi M, et al. Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: a comparison with 18F-FDG and 18F-FLT. J Nucl Med 2008;49:135–41.

    Article  PubMed  CAS  Google Scholar 

  21. Yi M, Kohanawa M, Ozaki M, Haga S, Fujikawa K, Zhao S, et al. Mutual modulation between interleukin-10 and interleukin-6 induced by Rhodococcus aurantiacus infection in mice. Microbes Infect 2008;10:1450–8.

    Article  Google Scholar 

  22. Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med 2001;42:1412–7.

    PubMed  CAS  Google Scholar 

  23. Lowe VJ, DeLong DM, Hoffman JM, Coleman RE. Optimum scanning protocol for FDG-PET evaluation of pulmonary malignancy. J Nucl Med 1995;36:883–7.

    PubMed  CAS  Google Scholar 

  24. Zhao S, Kuge Y, Tsukamoto E, Mochizuki T, Kato T, Hikosaka K, et al. Effects of insulin and glucose loading on FDG uptake in experimental malignant tumours and inflammatory lesions. Eur J Nucl Med 2001;28:730–5.

    Article  PubMed  CAS  Google Scholar 

  25. Ito T, Mitui H, Udaka N, Hayashi H, Okudela K, Kanisawa M, et al. Ki-67 (MIB 5) immunostaining of mouse lung tumors induced by 4-nitroquinoline 1-oxide. Histochem Cell Biol 1998;110:589–93.

    Article  PubMed  CAS  Google Scholar 

  26. Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med 2001;42:432–45.

    PubMed  CAS  Google Scholar 

  27. Stöber B, Tanase U, Herz M, Seidl C, Schwaiger M, Senekowitsch-Schmidtke R. Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells. Eur J Nucl Med Mol Imaging 2006;33:932–9.

    Article  PubMed  Google Scholar 

  28. Verrey F. System L: heteromeric exchangers of large, neutral amino acids involved in directional transport. Pflugers Arch 2003;445:529–33.

    PubMed  CAS  Google Scholar 

  29. Christensen HN. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev 1990;70:43–77.

    PubMed  CAS  Google Scholar 

  30. Kubota K, Matsuzawa T, Fujiwara T, Sato T, Tada M, Ido T, et al. Differential diagnosis of AH109A tumor and inflammation by radioscintigraphy with L-[methyl-11C]methionine. Jpn J Cancer Res 1989;80:778–82.

    PubMed  CAS  Google Scholar 

  31. Iuchi T, Iwadate Y, Namba H, Osato K, Saeki N, Yamaura A, et al. Glucose and methionine uptake and proliferative activity in meningiomas. Neurol Res 1999;21:640–4.

    PubMed  CAS  Google Scholar 

  32. Zhao S, Kuge Y, Kohanawa M, Zhao Y, Kanegae K, Seki K, et al. Usefulness of 11C-methionine in evaluating cellular proliferation and differential diagnosis of tumor and granuloma: an experimental study in comparison with 18F-FDG [abstract]. J Nucl Med 2007;48(Suppl 2):29P.

    Google Scholar 

  33. Osman S, Danpure HJ. The use of 2-[18F]fluoro-2-deoxy-D-glucose as a potential in vitro agent for labelling human granulocytes for clinical studies by positron emission tomography. Int J Rad Appl Instrum B 1992;19:183–90.

    PubMed  CAS  Google Scholar 

  34. Borregaard N, Herlin T. Energy metabolism of human neutrophils during phagocytosis. J Clin Invest 1982;70:550–7.

    Article  PubMed  CAS  Google Scholar 

  35. Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33:1972–80.

    PubMed  CAS  Google Scholar 

  36. Wang TC, Hsiao IT, Cheng YK, Wey SP, Yen TC, Lin KJ. Noninvasive monitoring of tumor growth in a rat glioma model: comparison between neurological assessment and animal imaging. J Neurooncol 2011. Feb 12. [Epub ahead of print].

  37. Asano M, Kohanawa M, Minagawa T, Nakane A. Reciprocal action of interferon-γ and interleukin-4 promotes granulomatous inflammation induced by Rhodococcus aurantiacus in mice. Immunology 1996;88:394–9.

    Article  PubMed  CAS  Google Scholar 

  38. Asano M, Nakae A, Minagawa T. Endogenous gamma interferon is essential in granuloma formation induced by glycolipid-containing mycolic acid in mice. Infect Immun 1993;61:2872–8.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was performed through Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. This work was also supported in part by grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science and from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors are grateful to the staff members of the Department of Nuclear Medicine, Central Institute of Isotope Science and Institute for Animal Experimentation, Hokkaido University, and the Facility of Radiology, Hokkaido University Hospital, for supporting this study. We also thank Ms. Eriko Suzuki and Koutarou Suzuki for continuously supporting this study and Kyotarou Suzuma, SHI Accelerator Service Ltd., for 18F-FDG and 11C-MET synthesis.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Songji Zhao, Yan Zhao, Keiichi Magota & Nagara Tamaki

  2. Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Songji Zhao & Yan Zhao

  3. Central Institute of Isotope Science, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Yuji Kuge & Toshiyuki Hatano

  4. Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Min Yi & Masashi Kohanawa

  5. Department of Molecular Imaging, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Ken-ichi Nishijima

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  1. Songji Zhao
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Correspondence to Yuji Kuge.

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Zhao, S., Kuge, Y., Yi, M. et al. Dynamic 11C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET. Eur J Nucl Med Mol Imaging 38, 1876–1886 (2011). https://doi.org/10.1007/s00259-011-1865-2

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  • DOI: https://doi.org/10.1007/s00259-011-1865-2

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