Clinical Value of Fluorine-18α-methyltyrosine PET in Patients with Gliomas: Comparison with Fluorine-18 Fluorodeoxyglucose PET

Overview

Journal EJNMMI Res

Date 2017 Jun 2

PMID 28567708

Citations 3

Authors

Keishi Horiguchi

Masahiko Tosaka

Tetsuya Higuchi

Yukiko Arisaka

Kenichi Sugawara

Junko Hirato

Hideaki Yokoo

Yoshito Tsushima

Yuhei Yoshimoto

Affiliations

Soon will be listed here.

Abstract

Background: We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose (F-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 F-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 F-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 F-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 F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of F-FDG PET was positively correlated (r = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of F-FDG and F-FAMT (r = 0.454, p = 0.004), but median T/N ratio of F-FAMT PET was significantly higher than that of F-FDG PET in all grades of glioma.

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

Citing Articles

LAT1-specific PET radiotracers: Development and clinical experiences of a new class of cancer-specific radiopharmaceuticals.

Achmad A, Hanaoka H, Holik H, Endo K, Tsushima Y, Kartamihardja A Theranostics. 2025; 15(5):1864-1878.

PMID: 39897549 PMC: 11780518. DOI: 10.7150/thno.99490.

Reply to the letter regarding "Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients-a report of the PET/RANO group": 18F-fluciclovine and target volume delineation.

Galldiks N, Niyazi M, Tonn J, Langen K Neuro Oncol. 2021; 23(8):1410-1411.

PMID: 34081114 PMC: 8328023. DOI: 10.1093/neuonc/noab098.

Targeted alpha therapy using astatine (At)-labeled phenylalanine: A preclinical study in glioma bearing mice.

Watabe T, Kaneda-Nakashima K, Shirakami Y, Liu Y, Ooe K, Teramoto T Oncotarget. 2020; 11(15):1388-1398.

PMID: 32341757 PMC: 7170498. DOI: 10.18632/oncotarget.27552.

New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma.

Verhoeven J, Hulpia F, Kersemans K, Bolcaen J, De Lombaerde S, Goeman J Sci Rep. 2019; 9(1):2878.

PMID: 30814660 PMC: 6393465. DOI: 10.1038/s41598-019-40013-x.

References

Pirotte B, Goldman S, Massager N, David P, Wikler D, Lipszyc M . Combined use of 18F-fluorodeoxyglucose and 11C-methionine in 45 positron emission tomography-guided stereotactic brain biopsies. J Neurosurg. 2004; 101(3):476-83. DOI: 10.3171/jns.2004.101.3.0476. View

Tripathi M, Sharma R, Dsouza M, Jaimini A, Panwar P, Varshney R . 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. 2010; 34(12):878-83. DOI: 10.1097/RLU.0b013e3181becfe0. View

Shinozaki N, Uchino Y, Yoshikawa K, Matsutani T, Hasegawa A, Saeki N . Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of 11C-methionine positron emission tomography. J Neurosurg. 2011; 114(6):1640-7. DOI: 10.3171/2010.11.JNS10553. View

Louis D, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee W . The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016; 131(6):803-20. DOI: 10.1007/s00401-016-1545-1. View

Glaudemans A, Enting R, Heesters M, Dierckx R, van Rheenen R, Walenkamp A . Value of 11C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imaging. 2012; 40(4):615-35. DOI: 10.1007/s00259-012-2295-5. View

Gulyas B, Halldin C . New PET radiopharmaceuticals beyond FDG for brain tumor imaging. Q J Nucl Med Mol Imaging. 2012; 56(2):173-90. View

Langen K, Tonn J, 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(3):665-6. DOI: 10.1007/s11060-014-1594-z. View

Ohtani T, Kurihara H, Ishiuchi S, Saito N, Oriuchi N, Inoue T . Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging. Eur J Nucl Med. 2001; 28(11):1664-70. DOI: 10.1007/s002590100620. View

Lau E, Drummond K, Ware R, Drummond E, Hogg A, Ryan G . Comparative PET study using F-18 FET and F-18 FDG for the evaluation of patients with suspected brain tumour. J Clin Neurosci. 2009; 17(1):43-9. DOI: 10.1016/j.jocn.2009.05.009. View

10.

Kato T, Shinoda J, Oka N, Miwa K, Nakayama N, Yano H . Analysis of 11C-methionine uptake in low-grade gliomas and correlation with proliferative activity. AJNR Am J Neuroradiol. 2008; 29(10):1867-71. PMC: 8118949. DOI: 10.3174/ajnr.A1242. View

11.

Inoue T, Koyama K, Oriuchi N, Alyafei S, Yuan Z, Suzuki H . Detection of malignant tumors: whole-body PET with fluorine 18 alpha-methyl tyrosine versus FDG--preliminary study. Radiology. 2001; 220(1):54-62. DOI: 10.1148/radiology.220.1.r01jl1654. View

12.

Langen K, Watts C . Neuro-oncology: Amino acid PET for brain tumours - ready for the clinic?. Nat Rev Neurol. 2016; 12(7):375-6. DOI: 10.1038/nrneurol.2016.80. View

13.

Kaira K, Oriuchi N, Otani Y, Shimizu K, Tanaka S, Imai H . Fluorine-18-alpha-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer: a clinicopathologic study. Clin Cancer Res. 2007; 13(21):6369-78. DOI: 10.1158/1078-0432.CCR-07-1294. View

14.

Suzuki S, Kaira K, Ohshima Y, Ishioka N, Sohda M, Yokobori T . Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer. Br J Cancer. 2014; 110(8):1985-91. PMC: 3992502. DOI: 10.1038/bjc.2014.142. View

15.

Tomiyoshi K, Amed K, Muhammad S, Higuchi T, Inoue T, Endo K . 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(2):169-75. DOI: 10.1097/00006231-199702000-00013. View

16.

Pauleit D, Floeth F, Hamacher K, Riemenschneider M, Reifenberger G, Muller H . O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain. 2005; 128(Pt 3):678-87. DOI: 10.1093/brain/awh399. View

17.

Habermeier A, Graf J, Sandhofer B, Boissel J, Roesch F, Closs E . System L amino acid transporter LAT1 accumulates O-(2-fluoroethyl)-L-tyrosine (FET). Amino Acids. 2014; 47(2):335-44. DOI: 10.1007/s00726-014-1863-3. View

18.

Kaira K, Oriuchi N, Shimizu K, Tominaga H, Yanagitani N, Sunaga N . 18F-FMT uptake seen within primary cancer on PET helps predict outcome of non-small cell lung cancer. J Nucl Med. 2009; 50(11):1770-6. DOI: 10.2967/jnumed.109.066837. View

19.

Inoue T, Shibasaki T, Oriuchi N, Aoyagi K, Tomiyoshi K, Amano S . 18F alpha-methyl tyrosine PET studies in patients with brain tumors. J Nucl Med. 1999; 40(3):399-405. View

20.

Albert N, Winkelmann I, Suchorska B, Wenter V, Schmid-Tannwald C, Mille E . 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. 2015; 43(6):1105-14. DOI: 10.1007/s00259-015-3276-2. View