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Diagnostic performance of 18F-fluorothymidine PET/CT for primary colorectal cancer and its lymph node metastasis: comparison with 18F-fluorodeoxyglucose PET/CT

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To examine the diagnostic performance of 18F-fluorothymidine (FLT) PET/CT in primary and metastatic lymph node colorectal cancer foci in comparison with 18F-fluorodeoxyglucose (FDG) PET/CT.

Methods

The study population comprised 28 patients with 30 newly diagnosed colorectal cancers who underwent surgical resection of the primary lesion and regional lymph nodes after both FLT and FDG PET/CT. The associations between SUVmax levels and pathological factors were evaluated using the Mann-Whitney U or Kruskal-Wallis test. Differences in diagnostic indexes for detecting nodal metastasis between the two tracers were estimated using the McNemar exact or χ 2 test.

Results

All 30 primary cancers (43.0 ± 20.0 mm, range 14 – 85 mm) were visualized by both tracers, but none of the FLT SUVmax values exceeded the FDG SUVmax values in any of the primary cancers (6.6 ± 2.4 vs. 13.6 ± 5.8, p < 0.001). The sensitivity, specificity and accuracy for detecting nodal metastasis were 41 % (15/37), 98.8 % (493/499) and 94.8 % (508/536) for FDG PET/CT, and 32 % (12/37), 98.8 % (493/499) and 94.2 % (505/536) for FLT PET/CT, respectively. The sensitivity (p = 0.45), specificity (p = 0.68) and accuracy (p = 0.58) were not different between the tracers. Nodal uptake of FLT and FDG was discordant in 7 (19 %) of 37 metastatic nodes. There were ten concordant true-positive nodes of which six showed higher FDG SUVmax and four showed higher FLT SUVmax, but the difference between FDG and FLT SUVmax was not significant (5.56 ± 3.55 and 3.62 ± 1.45, respectively; p = 0.22).

Conclusion

FLT has the same potential as FDG in PET/CT for the diagnosis of primary and nodal foci of colorectal cancer despite significantly lower FLT uptake in primary foci.

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References

  1. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22:191–7.

    Article  PubMed  Google Scholar 

  2. Iyer RB, Silverman PM, Dubrow RA, Charnsangavej C. Imaging in the diagnosis, staging, and follow-up of colorectal cancer. AJR Am J Roentgenol. 2002;179:3–13.

    Article  PubMed  Google Scholar 

  3. Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 2008;49:480–508.

    Article  PubMed  Google Scholar 

  4. von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and future directions. Radiology. 2006;238:405–22.

    Article  Google Scholar 

  5. Cohade C, Osman M, Leal J, Whal RL. Direct comparison of 18F-FDG PET and PET/CT in patients with colorectal carcinoma. J Nucl Med. 2003;44:1797–803.

    PubMed  Google Scholar 

  6. Delbeke D, Martin W. PET and PET-CT for evaluation of colorectal carcinoma. Semin Nucl Med. 2004;34:209–23.

    Article  PubMed  Google Scholar 

  7. Park IJ, Kim HC, Yu CS, Ryu MH, Chang HM, Kim JH, et al. Efficacy of PET/CT in the accurate evaluation of primary colorectal carcinoma. Eur J Surg Oncol. 2006;32:941–7.

    Article  PubMed  CAS  Google Scholar 

  8. Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med. 1998;4:1334–6.

    Article  PubMed  CAS  Google Scholar 

  9. Rasey JS, Grierson JR, Wiens LW, Kolb PD, Schwartz JL. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med. 2002;43:1210–7.

    PubMed  CAS  Google Scholar 

  10. Bading JR, Shields AF. Imaging of cell proliferation: status and prospects. J Nucl Med. 2008;49:64s–80.

    Article  PubMed  CAS  Google Scholar 

  11. Francis DL, Visvikis D, Costa DC, Arulampalam TH, Townsend C, Luthra SK, et al. Potential impact of [18F]3′-deoxy-3′-fluorothymidine versus [18F]fluror-2-deoxy-D-glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging. 2003;30:988–94.

    Article  PubMed  CAS  Google Scholar 

  12. Francis DL, Freeman A, Visvikis D, Costa DC, Luthra SK, Novelli M, et al. In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography. Gut. 2003;52:1602–6.

    Article  PubMed  CAS  Google Scholar 

  13. Wieder HA, Geinitz H, Rosenberg R, Lordick F, Becker K, Stahl A, et al. PET imaging with [18F]3′-deoxy-3′-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer. Eur J Nucl Med Mol Imaging. 2007;34:878–83.

    Article  PubMed  CAS  Google Scholar 

  14. Yamamoto Y, Kameyama R, Izuishi K, Takebayashi R, Hagiike M, Asakura M, et al. Detection of colorectal cancer using 18F-FLT PET: comparison with 18F-FDG PET. Nucl Med Commun. 2009;30:841–5.

    Article  PubMed  Google Scholar 

  15. Muijs CT, Beukema JC, Widder J, van den Bergh AC, Havenga K, Pruim J, et al. 18F-FLT-PET for detection of rectal cancer. Radiother Oncol. 2011;98:357–9.

    Article  PubMed  Google Scholar 

  16. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Radiology. 2003;226:24–8.

    Article  PubMed  Google Scholar 

  17. Yamamoto Y, Nishiyama Y, Ishikawa S, Nakano J, Chang SS, Bandoh S, et al. Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2007;34:1610–6.

    Article  PubMed  CAS  Google Scholar 

  18. Menda Y, Boles Ponto LL, Dornfeld KJ, Tewson TJ, Watkins GL, Schultz MK, et al. Kinetic analysis of 3′-deox-3′-18F-fluoro-thymidine (18F-FLT) in head and neck cancer patients before and early after initiation of chemoradiation therapy. J Nucl Med. 2009;50:1028–35.

    Article  PubMed  CAS  Google Scholar 

  19. Hoshikawa H, Nishiyama Y, Kishino T, Yamamoto Y, Haba R, Mori N. Comparison of FLT-PET and FDG-PET for visualization of head and neck squamous cell cancers. Mol Imaging Biol. 2011;13:172–7.

    Article  PubMed  Google Scholar 

  20. Oh SJ, Mosdzianowski C, Chi DY, Kim JY, Kang SH, Ryu JS, et al. Fully automated synthesis system of 3′-deoxy-3′-[18F]fluorothymidine. Nucl Med Biol. 2004;31:803–9.

    Article  PubMed  CAS  Google Scholar 

  21. American Joint Committee on Cancer. AJCC cancer staging manual. 6th ed. Berlin: Springer; 2002. p. 113–23.

    Google Scholar 

  22. Tian J, Yang X, Yu L, Chen P, **n J, Ma L, et al. A multicenter clinical trial on the diagnostic value of dual-tracer PET/CT in pulmonary lesions using 3′-deoxy-3′-18F-fluorothymidine and 18F-FDG. J Nucl Med. 2008;49:186–94.

    Article  PubMed  Google Scholar 

  23. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.

    Article  PubMed  CAS  Google Scholar 

  24. Been LB, Suurmeijer AJ, Cobben DC, Jager PL, Hoekstra HJ, Elsinga PH. [18F]FLT-PET in oncology: current status and opportunities. Eur J Nucl Med Mol Imaging. 2004;31:1659–72.

    Article  PubMed  Google Scholar 

  25. Romero-Garcia S, Lopez-Gonzalez JS, Baez-Viveros JL, Aguilar-Cazares D, Prado-Garcia H. Tumor cell metabolism: an integral view. Cancer Biol Ther. 2011;12:939–48.

    PubMed  CAS  Google Scholar 

  26. Kubota K, Kubota R, Yamada S. FDG accumulation in tumor tissue. J Nucl Med. 1993;34:419–21.

    PubMed  CAS  Google Scholar 

  27. Higashi K, Clavo AC, Wahl RL. Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. J Nucl Med. 1993;34:414–9.

    PubMed  CAS  Google Scholar 

  28. van Westreenen HL, Cobben DC, Jager PL, van Dullemen HM, Wesseling J, Elsinga PH, et al. Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer. J Nucl Med. 2005;46:400–4.

    PubMed  Google Scholar 

  29. Huang T, Civelek AC, Li J, Jiang H, Ng CK, Postel GC, et al. Tumor microenvironment-dependent 18F-FDG, 18F-fluorothymidine, and 18F-misonidazole uptake: a pilot study in mouse models of human non-small cell lung cancer. J Nucl Med. 2012;53:1262–8.

    Article  PubMed  CAS  Google Scholar 

  30. Izuishi K, Yamamoto Y, Sano T, Takebayashi R, Nishiyama Y, Mori H, et al. Molecular mechanism underlying the detection of colorectal cancer by 18F-2-fluoro2-deoxy-d-glucose positron emission tomography. J Gastrointest Surg. 2012;16:394–400.

    Article  PubMed  Google Scholar 

  31. Hong R, Lim SC. 18F-fluoro-2-deoxyglucose uptake on PET CT and glucose transporter 1 expression in colorectal adenocarcinoma. World J Gastroenterol. 2012;18:168–74.

    Article  PubMed  CAS  Google Scholar 

  32. Gu J, Yamamoto H, Fukunaga H, Danno K, Takemasa I, Ikeda M, et al. Correlation of GLUT-1 overexpression, tumor size, and depth of invasion with 18F-2-fluoro2-deoxy-D-glucose uptake by positron emission tomography in colorectal cancer. Dig Dis Sci. 2006;51:2198–205.

    Article  PubMed  CAS  Google Scholar 

  33. Mainenti PP, Iodice D, Segreto S, Storto G, Magliulo M, De Palma GD, et al. Colorectal cancer and 18FDG-PET/CT: what about adding the T to the N parameter in loco-regional staging? World J Gastroenterol. 2011;17:1427–33.

    Article  PubMed  Google Scholar 

  34. Tsujikawa T, Otsuka H, Morita N, Saegusa H, Kobayashi M, Okazawa H, et al. Does partial volume corrected maximum SUV based on count recovery coefficient in 3D-PET/CT correlate with clinical aggressiveness of non-Hodgkin’s lymphoma? Ann Nucl Med. 2008;22:23–30.

    Article  PubMed  Google Scholar 

  35. Kubota K. From tumor biology to clinical PET: a review of positron emission tomography (PET) in oncology. Ann Nucl Med. 2001;15:471–86.

    Article  PubMed  CAS  Google Scholar 

  36. 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 

  37. Konishi T, Miyama T, Sakamoto S, Hirata T, Mafune K, Hiraishi M, et al. Activities of thymidylate synthetase and thymidine kinase in gastric cancer. Surg Oncol. 1992;1:215–21.

    Article  PubMed  CAS  Google Scholar 

  38. Tsunoda Y, Ito M, Fujii H, Kuwano H, Saito N. Preoperative diagnosis of lymph node metastases of colorectal cancer by FDG-PET/CT. Jpn J Clin Oncol. 2008;38:347–53.

    Article  PubMed  Google Scholar 

  39. Troost EG, Vogel WV, Merkx MA, Slootweg PJ, Marres HA, Peeters WJ, et al. 18F-FLT PET does not discriminate between reactive and metastatic lymph nodes in primary head and neck cancer patients. J Nucl Med. 2007;48:726–35.

    Article  PubMed  Google Scholar 

  40. Hui W, **ming Z, Jiahe T, Baolin Q, Tianran L, Yingmao C, et al. Using dual-tracer PET to predict the biologic behavior of human colorectal cancer. J Nucl Med. 2009;50:1857–64.

    Article  Google Scholar 

  41. Dittmann H, Dohmen BM, Kehlbach R, Bartusek G, Pritzkow M, Sarbia M, et al. Early change in [18F]FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med. 2002;29:1462–9.

    Article  CAS  Google Scholar 

  42. Mudd SR, Holich KD, Voorbach MJ, Cole TB, Reuter DR, Tapang P, et al. Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model. Mol Imaging Biol. 2012;14:617–24.

    Article  PubMed  Google Scholar 

  43. Pio BS, Park CK, Pietras R, Hsueh WA, Satyamurthy N, Pegram MD, et al. Usefulness of 3′-[F-18]fluoro-3′-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol. 2006;8:36–42.

    Article  PubMed  Google Scholar 

  44. Kishino T, Hoshikawa H, Nishiyama Y, Yamamoto Y, Mori N. Usefulness of 3′-deoxy-3′-18F-fluorothymidine PET for predicting early response to chemoradiotherapy in head and neck cancer. J Nucl Med. 2012;53:1521–7.

    Article  PubMed  CAS  Google Scholar 

  45. Graf N, Herrmann K, Numberger B, Zwisler D, Aichler M, Feuchtinger A, et al. [18F]FLT is superior to [18F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner. Eur J Nucl Med Mol Imaging. 2013;40:34–43.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiology, Kagoshima University, Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Masatoyo Nakajo, Masayuki Nakajo, Megumi **guji & Yoshihiko Fukukura

  2. Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan

    Masatoyo Nakajo, Yoriko Kajiya & Atushi Tani

  3. Department of Gastroenterology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan

    Nobuaki Nishimata, Shunji Shimaoka & Tohru Nihara

  4. Department of Surgery, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan

    Kuniaki Aridome

  5. Department of Pathology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan

    Sadao Tanaka

  6. Department of Epidemiology and Preventive Medicine, Kagoshima University, Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Chihaya Koriyama

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  1. Masatoyo Nakajo
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Correspondence to Masatoyo Nakajo.

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Nakajo, M., Nakajo, M., Kajiya, Y. et al. Diagnostic performance of 18F-fluorothymidine PET/CT for primary colorectal cancer and its lymph node metastasis: comparison with 18F-fluorodeoxyglucose PET/CT. Eur J Nucl Med Mol Imaging 40, 1223–1232 (2013). https://doi.org/10.1007/s00259-013-2424-9

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