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Open Access 01-12-2017 | Original research

Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET

Authors: Keishi Horiguchi, Masahiko Tosaka, Tetsuya Higuchi, Yukiko Arisaka, Kenichi Sugawara, Junko Hirato, Hideaki Yokoo, Yoshito Tsushima, Yuhei Yoshimoto

Published in: EJNMMI Research | Issue 1/2017

Abstract

Background

We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (¹⁸F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) PET in 38 consecutive glioma patients. The tumor to normal brain ratios (T/N ratios) were calculated, and the relationships between T/N ratio and World Health Organization tumor grade or MIB-1 labeling index were evaluated. The diagnostic values of T/N ratios were assessed using receiver operating characteristic (ROC) curve analyses to differentiate between high-grade gliomas (HGGs) and low-grade gliomas (LGGs).

Results

Median T/N ratio of ¹⁸F-FAMT PET was 2.85, 4.65, and 4.09 for grade II, III, and IV gliomas, respectively, with significant differences between HGGs and LGGs (p = 0.006). Both T/N ratio (p = 0.016) and maximum standardized uptake value (p = 0.033) of ¹⁸F-FDG PET showed significant differences between HGGs and LGGs. ROC analysis yielded an optimal cut-off of 3.37 for the T/N ratio of ¹⁸F-FAMT PET to differentiate between HGGs and LGGs (sensitivity 81%, specificity 67%, accuracy 76%, area under the ROC curve 0.776). Positive predictive value was 84%, and negative predictive value was 62%. T/N ratio of ¹⁸F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of ¹⁸F-FDG PET was positively correlated (r _s = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of ¹⁸F-FDG and ¹⁸F-FAMT (r _s = 0.454, p = 0.004), but median T/N ratio of ¹⁸F-FAMT PET was significantly higher than that of ¹⁸F-FDG PET in all grades of glioma.

Conclusions

The T/N ratio of ¹⁸F-FAMT uptake has high positive predictive value for detection of HGGs. ¹⁸F-FAMT PET had higher T/N ratio, with better tumor-normal brain contrast, compared to ¹⁸F-FDG PET in both LGGs and HGGs. Therefore, ¹⁸F-FAMT is a useful radiotracer for the preoperative visualization of gliomas.

Di Chiro G, Brooks RA. PET-FDG of untreated and treated cerebral gliomas. J Nucl Med. 1988;29:421–3.PubMed

Gulyás B, Halldin C. New PET radiopharmaceuticals beyond FDG for brain tumor imaging. Q J Nucl Med Mol Imaging. 2012;56:173–90.PubMed

Albert NL, Weller M, Suchorska B, Galldiks N, Soffietti R, Kim MM, et al. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro Oncol. 2016;18:1199–208.CrossRefPubMed

Langen KJ, Watts C. Neuro-oncology: amino acid PET for brain tumours—ready for the clinic? Nat Rev Neurol. 2016;12:375–6.CrossRefPubMed

Shinozaki N, Uchino Y, Yoshikawa K, Matsutani T, Hasegawa A, Saeki N, et al. Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of ¹¹C-methionine positron emission tomography. J Neurosurg. 2011;114:1640–7.CrossRefPubMed

Glaudemans AW, Enting RH, Heesters MA, Dierckx RA, van Rheenen RW, Walenkamp AM, et al. Value of ¹¹C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imaging. 2013;40:615–35.CrossRefPubMed

Ohtani T, Kurihara H, Ishiuchi S, Saito N, Oriuchi N, Inoue T, et al. Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging. Eur J Nucl Med. 2001;28:1664–70.CrossRefPubMed

Weber WA, Wester HJ, Grosu AL, Herz M, Dzewas B, Feldmann HJ, et al. O-(2-[¹⁸F]fluoroethyl)-L-tyrosine and L-[methyl-¹¹C]methionine uptake in brain tumours: initial results of a comparative study. Eur J Nucl Med. 2000;27:542–9.CrossRefPubMed

Floeth FW, Pauleit D, Wittsack HJ, Langen KJ, Reifenberger G, Hamacher K, et al. Multimodal metabolic imaging of cerebral gliomas: positron emission tomography with [¹⁸F]fluoroethyl-L-tyrosine and magnetic resonance spectroscopy. J Neurosurg. 2005;102:318–27.CrossRefPubMed

10.

Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Müller HW, et al. O-(2-[¹⁸F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128:678–87.CrossRefPubMed

11.

Kratochwil C, Combs SE, Leotta K, Afshar-Oromieh A, Rieken S, Debus J, et al. Intra-individual comparison of ¹⁸F-FET and ¹⁸F-DOPA in PET imaging of recurrent brain tumors. Neuro Oncol. 2014;16:434–40.CrossRefPubMed

12.

Tripathi M, Sharma R, D’Souza M, Jaimini A, Panwar P, Varshney R, et al. Comparative evaluation of F-18 FDOPA, F-18 FDG, and F-18 FLT-PET/CT for metabolic imaging of low grade gliomas. Clin Nucl Med. 2009;34:878–83.CrossRefPubMed

13.

Langen KJ, Tonn JC, Weller M, Galldiks N. Letter to the Editor: “The role of imaging in the management of progressive glioblastoma. A systematic review and evidence-based clinical practice guideline” [J Neurooncol 2014;118:435–460]. J Neurooncol. 2014;120:665–6.CrossRefPubMed

14.

Tomiyoshi K, Amed K, Muhammad S, Higuchi T, Inoue T, Endo K, et al. Synthesis of isomers of ¹⁸F-labelled amino acid radiopharmaceutical: position 2- and 3-L-¹⁸F-alpha-methyltyrosine using a separation and purification system. Nucl Med Commun. 1997;18:169–75.CrossRefPubMed

15.

Inoue T, Tomiyoshi K, Higuichi T, Ahmed K, Sarwar M, Aoyagi K, et al. Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent. J Nucl Med. 1998;39:663–7.PubMed

16.

Kaira K, Oriuchi N, Otani Y, Shimizu K, Tanaka S, Imai H, et al. Fluorine-18-alpha-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer: a clinicopathologic study. Clin Cancer Res. 2007;13:6369–78.CrossRefPubMed

17.

Kaira K, Oriuchi N, Shimizu K, Tominaga H, Yanagitani N, Sunaga N, et al. ¹⁸F-FMT uptake seen within primary cancer on PET helps predict outcome of non-small cell lung cancer. J Nucl Med. 2009;50:1770–6.CrossRefPubMed

18.

Kaira K, Oriuchi N, Shimizu K, Ishikita T, Higuchi T, Imai H, et al. Evaluation of thoracic tumors with (18)F-FMT and (18)F-FDG PET-CT: a clinicopathological study. Int J Cancer. 2009;124:1152–60.CrossRefPubMed

19.

Miyashita G, Higuchi T, Oriuchi N, Arisaka Y, Hanaoka H, Tominaga H, et al. ¹⁸F-FAMT uptake correlates with tumor proliferative activity in oral squamous cell carcinoma: comparative study with ¹⁸F-FDG PET and immunohistochemistry. Ann Nucl Med. 2010;24:579–84.CrossRefPubMed

20.

Suzuki S, Kaira K, Ohshima Y, Ishioka NS, Sohda M, Yokobori T, et al. Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer. Br J Cancer. 2014;110:1985–91.CrossRefPubMedPubMedCentral

21.

Inoue T, Shibasaki T, Oriuchi N, Aoyagi K, Tomiyoshi K, Amano S, et al. ¹⁸F alpha-methyl tyrosine PET studies in patients with brain tumors. J Nucl Med. 1999;40:399–405.PubMed

22.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.CrossRefPubMedPubMedCentral

23.

Inoue T, Koyama K, Oriuchi N, Alyafei S, Yuan Z, Suzuki H, et al. Detection of malignant tumors: whole-body PET with fluorine 18 alpha-methyl tyrosine versus FDG--preliminary study. Radiology. 2001;220:54–62.CrossRefPubMed

24.

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131:803–20.CrossRefPubMed

25.

Kaschten B, Stevenaert A, Sadzot B, Deprez M, Degueldre C, Del Fiore G, et al. Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med. 1998;39:778–85.PubMed

26.

Kato T, Shinoda J, Oka N, Miwa K, Nakayama N, Yano H, et al. Analysis of ¹¹C-methionine uptake in low-grade gliomas and correlation with proliferative activity. AJNR Am J Neuroradiol. 2008;29:1867–71.CrossRefPubMed

27.

Kato T, Shinoda J, Nakayama N, Miwa K, Okumura A, Yano H, et al. Metabolic assessment of gliomas using ¹¹C-methionine, [¹⁸F]fluorodeoxyglucose, and ¹¹C-choline positron-emission tomography. AJNR Am J Neuroradiol. 2008;29:1176–82.CrossRefPubMed

28.

Derlon JM, Petit-Taboué MC, Chapon F, Beaudouin V, Noël MH, Creveuil C, et al. The in vivo metabolic pattern of low-grade brain gliomas: a positron emission tomographic study using ¹⁸F-fluorodeoxyglucose and ¹¹C-L-methylmethionine. Neurosurgery. 1997;40:276–87. discussion 287–8.CrossRefPubMed

29.

Langen KJ, Mühlensiepen H, Holschbach M, Hautzel H, Jansen P, Coenen HH. Transport mechanisms of 3-[¹²³I]iodo-alpha-methyl-L-tyrosine in a human glioma cell line: comparison with [³H]methyl]-L-methionine. J Nucl Med. 2000;41:1250–5.PubMed

30.

Langen KJ, Ziemons K, Kiwit JC, Herzog H, Kuwert T, Bock WJ, et al. 3-[¹²³I]iodo-alpha-methyltyrosine and [methyl-¹¹C]-L-methionine uptake in cerebral gliomas: a comparative study using SPECT and PET. J Nucl Med. 1997;38:517–22.PubMed

31.

Kobayashi K, Ohnishi A, Promsuk J, Shimizu S, Kanai Y, Shiokawa Y, et al. Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells. Neurosurgery. 2008;62:493–503. discussion 503–4.CrossRefPubMed

32.

Kaira K, Oriuchi N, Imai H, Shimizu K, Yanagitani N, Sunaga N, et al. L-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms. Cancer Sci. 2008;99:2380–6.CrossRefPubMed

33.

Okubo S, Zhen HN, Kawai N, Nishiyama Y, Haba R, Tamiya T. Correlation of L-methyl-¹¹C-methionine (MET) uptake with L-type amino acid transporter 1 in human gliomas. J Neurooncol. 2010;99:217–25.CrossRefPubMed

34.

Wiriyasermkul P, Nagamori S, Tominaga H, Oriuchi N, Kaira K, Nakao H, et al. Transport of 3-fluoro-L-α-methyl-tyrosine by tumor-upregulated L-type amino acid transporter 1: a cause of the tumor uptake in PET. J Nucl Med. 2012;53:1253–61.CrossRefPubMed

35.

Weckesser M, Langen KJ, Rickert CH, Kloska S, Straeter R, Hamacher K, et al. O-(2-[¹⁸F]fluorethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours. Eur J Nucl Med Mol Imaging. 2005;32:422–9.CrossRefPubMed

36.

Habermeier A, Graf J, Sandhofer BF, Boissel JP, Roesch F, Closs EI. System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine (FET). Amino Acids. 2015;47:335–44.CrossRefPubMed

37.

Albert NL, Winkelmann I, Suchorska B, Wenter V, Schmid-Tannwald C, Mille E, et al. Early static (18)F-FET-PET scans have a higher accuracy for glioma grading than the standard 20–40 min scans. Eur J Nucl Med Mol Imaging. 2016;43:1105–14.CrossRefPubMed

38.

Goldman S, Levivier M, Pirotte B, Brucher JM, Wikler D, Damhaut P, et al. Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy. J Nucl Med. 1997;38:1459–62.PubMed

39.

Pirotte B, Goldman S, David P, Wikler D, Damhaut P, Vandesteene A, et al. Stereotactic brain biopsy guided by positron emission tomography (PET) with [F-18]fluorodeoxyglucose and [C-11]methionine. Acta Neurochir Suppl. 1997;68:133–8.PubMed

40.

Pirotte B, Goldman S, Massager N, David P, Wikler D, Lipszyc M, et al. Combined use of ¹⁸F-fluorodeoxyglucose and ¹¹C-methionine in 45 positron emission tomography-guided stereotactic brain biopsies. J Neurosurg. 2004;101:476–83.CrossRefPubMed

41.

Spaeth N, Wyss MT, Weber B, Scheidegger S, Lutz A, Verwey J, et al. Uptake of ¹⁸F-fluorocholine, ¹⁸F-fluoroethyl-L-tyrosine, and ¹⁸F-FDG in acute cerebral radiation injury in the rat: implications for separation of radiation necrosis from tumor recurrence. J Nucl Med. 2004;45:1931–8.PubMed

42.

Van Laere K, Ceyssens S, Van Calenbergh F, de Groot T, Menten J, Flamen P, et al. Direct comparison of ¹⁸F-FDG and ¹¹C-methionine PET in suspected recurrence of glioma: sensitivity, inter-observer variability and prognostic value. Eur J Nucl Med Mol Imaging. 2005;32:39–51.CrossRefPubMed

43.

Pauleit D, Stoffels G, Bachofner A, Floeth FW, Sabel M, Herzog H, et al. Comparison of (18)F-FET and (18)F-FDG PET in brain tumors. Nucl Med Biol. 2009;36:779–87.CrossRefPubMed

44.

Lau EW, Drummond KJ, Ware RE, Drummond E, Hogg A, Ryan G, et al. Comparative PET study using F-18 FET and F-18 FDG for the evaluation of patients with suspected brain tumour. J Clin Neurosci. 2010;17:43–9.CrossRefPubMed

45.

Plotkin M, Blechschmidt C, Auf G, Nyuyki F, Geworski L, Denecke T, et al. Comparison of F-18 FET-PET with F-18 FDG-PET for biopsy planning of non-contrast-enhancing gliomas. Euro Radiol. 2010;20:2496–502.CrossRef

46.

Miyake K, Shinomiya A, Okada M, Hatakeyama T, Kawai N, Tamiya T. Usefulness of FDG, MET and FLT-PET studies for the management of human gliomas. J Biomed Biotechnol. 2012;2012:205818.CrossRefPubMedPubMedCentral

47.

Tripathi M, Sharma R, Varshney R, Jaimini A, Jain J, Souza MM, et al. Comparison of F-18 FDG and C-11 methionine PET/CT for the evaluation of recurrent primary brain tumors. Clin Nucl Med. 2012;37:158–63.CrossRefPubMed

48.

Galldiks N, Langen KJ. Applications of PET imaging of neurological tumors with radiolabeled amino acids. Q J Nucl Med Mol Imaging. 2015;59:70–82.PubMed

49.

Calcagni ML, Galli G, Giordano A, Taralli S, Anile C, Niesen A, et al. Dynamic O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (F-18 FET) PET for glioma grading: assessment of individual probability of malignancy. Clin Nucl Med. 2011;36:841–7.CrossRefPubMed

50.

Moulin-Romsee 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.CrossRefPubMed

Title: Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET
Authors: Keishi Horiguchi
Masahiko Tosaka
Tetsuya Higuchi
Yukiko Arisaka
Kenichi Sugawara
Junko Hirato
Hideaki Yokoo
Yoshito Tsushima
Yuhei Yoshimoto
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2017
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-017-0298-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET

Abstract

Background

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

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