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Open Access 01-12-2015 | Original research

Differentiation of malignant tumours from granulomas by using dynamic [¹⁸F]-fluoro-L-α-methyltyrosine positron emission tomography

Authors: Aiko Yamaguchi, Hirofumi Hanaoka, Yutaka Fujisawa, Songji Zhao, Kazutomo Suzue, Akihiro Morita, Hideyuki Tominaga, Tetsuya Higuchi, Hajime Hisaeda, Yoshito Tsushima, Yuji Kuge, Yasuhiko Iida

Published in: EJNMMI Research | Issue 1/2015

Abstract

Background

Previous clinical studies have revealed the potential of [¹⁸F]-fluoro-L-α-methyltyrosine (¹⁸F-FAMT) for the differential diagnosis of malignant tumours from sarcoidosis. However, one concern regarding the differential diagnosis with ¹⁸F-FAMT is the possibility of false negatives given the small absolute uptake of ¹⁸F-FAMT that has been observed in some malignant tumours. The aim of this study was to evaluate a usefulness of dynamic ¹⁸F-FAMT positron emission tomography (PET) for differentiating malignant tumours from granulomas.

Methods

Rats bearing both granulomas (Mycobacterium bovis bacillus Calmette-Guérin (BCG)-induced) and tumours (C6 glioma cell-induced) underwent dynamic 2-deoxy-2-[¹⁸F]-fluoro-D-glucose (¹⁸F-FDG) PET and ¹⁸F-FAMT PET for 120 min on consecutive days. Time-activity curves, static images, mean standardized uptake values (SUVs) and the SUV ratios (SUVRs; calculated by dividing SUV at each time point by that of 2 min after injection) were assessed.

Results

In tumours, ¹⁸F-FAMT showed a shoulder peak immediately after the initial distribution followed by gradual clearance compared with granulomas. Although the mean SUV in the tumours (1.00 ± 0.10) was significantly higher than that in the granulomas (0.88 ± 0.12), a large overlap was observed. In contrast, the SUVR was markedly higher in tumours than in granulomas (50 min/2 min, 0.72 ± 0.06 and 0.56 ± 0.05, respectively) with no overlap. The dynamic patterns, SUVR, and mean SUV of ¹⁸F-FDG in the granulomas were comparable to those in the tumours.

Conclusions

Dynamic ¹⁸F-FAMT and SUVR analysis might compensate for the current limitations and help in improving the diagnostic accuracy of ¹⁸F-FAMT.

Larson SM. Cancer or inflammation? A holy grail for nuclear medicine. J Nucl Med. 1994;35:1653–5.PubMed

Endo K, Oriuchi N, Higuchi T, Iida Y, Hanaoka H, Miyakubo M, et al. PET and PET/CT using ¹⁸F-FDG in the diagnosis and management of cancer patients. Int J Clin Oncol. 2006;11:286–96.CrossRefPubMed

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

Lee TS, Ahn SH, Moon BS, Chun KS, Kang JH, Cheon GJ, et al. Comparison of ¹⁸F-FDG, ¹⁸F-FET and ¹⁸F-FLT for differentiation between tumor and inflammation in rats. Nucl Med Biol. 2009;36:681–6.CrossRefPubMed

Stober 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.CrossRefPubMed

Rau FC, Weber WA, Wester HJ, Herz M, Becker I, Kruger A, et al. O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes. Eur J Nucl Med Mol Imaging. 2002;29:1039–46.CrossRefPubMed

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.CrossRefPubMed

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

Wiriyasermkul P, Nagamori S, Tominaga H, Oriuchi N, Kaira K, Nakao H, et al. Transport of 3-fluoro-L-alpha-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

10.

Kaira K, Oriuchi N, Otani Y, Yanagitani N, Sunaga N, Hisada T, et al. Diagnostic usefulness of fluorine-18-alpha-methyltyrosine positron emission tomography in combination with ¹⁸F-Fluorodeoxyglucose in sarcoidosis patients. Chest. 2007;131:1019–27.CrossRefPubMed

11.

Zhao S, Kuge Y, Yi M, Zhao Y, Hatano T, Magota K, 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. 2011;38:1876–86.CrossRefPubMed

12.

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

13.

Hamacher KCH, Stöcklin G. Efficient stereospecific synthesis of no-carrier-added 2-[¹⁸F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med. 1986;27:235–8.PubMed

14.

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.CrossRefPubMed

15.

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.CrossRefPubMed

16.

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

17.

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

18.

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

19.

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

20.

Broer S. Amino acid transport across mammalian intestinal and renal epithelia. Physiol Rev. 2008;88:249–86.CrossRefPubMed

21.

Langen KJ, Muhlensiepen 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

22.

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

23.

Ohkame H, Masuda H, Ishii Y, Kanai Y. Expression of L-type amino acid transporter 1 (LAT1) and 4 F2 heavy chain (4F2hc) in liver tumor lesions of rat models. J Surg Oncol. 2001;78:265–71. discussion 271–2.CrossRefPubMed

24.

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

Title: Differentiation of malignant tumours from granulomas by using dynamic [18F]-fluoro-L-α-methyltyrosine positron emission tomography
Authors: Aiko Yamaguchi
Hirofumi Hanaoka
Yutaka Fujisawa
Songji Zhao
Kazutomo Suzue
Akihiro Morita
Hideyuki Tominaga
Tetsuya Higuchi
Hajime Hisaeda
Yoshito Tsushima
Yuji Kuge
Yasuhiko Iida
Publication date: 01-12-2015
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-015-0109-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Differentiation of malignant tumours from granulomas by using dynamic [¹⁸F]-fluoro-L-α-methyltyrosine positron emission tomography

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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