Diagnosis of Brain Tumors Using Amino Acid Transport PET Imaging with 18F-fluciclovine: A Comparative Study with L-methyl-11C-methionine PET Imaging

Naohiro Tsuyuguchi, Yuzo Terakawa, Takehiro Uda, Kosuke Nakajo, Yonehiro Kanemura, Naohiro Tsuyuguchi, Yuzo Terakawa, Takehiro Uda, Kosuke Nakajo, Yonehiro Kanemura

Abstract

Objectives: 18F-fluciclovine (trans-1-amino-3-[18F] fluorocyclobutanecarboxylic acid, [FACBC]) is an artificial amino acid radiotracer used for positron emission tomography (PET) studies, which is metabolically stable in vivo and has a long half-life. It has already been shown that FACBC-PET is useful for glioma imaging. However, there have been no reports evaluating the efficiency of FACBC-PET in the diagnosis of brain tumors in comparison with other PET tracers in clinical studies. The purpose of this study was to investigate the efficacy of FACBC-PET imaging in glioma diagnosis, compared to L-methyl- 11 C-methionine (MET)-PET.

Methods: Six consecutive patients (four male, two female), who were clinically suspected of having high- or low-grade glioma, received both FACBC-PET and MET-PET within a two-week interval. T1-weighted, contrast-enhanced, T1-weighted, and fluid-attenuated inversion recovery magnetic resonance imaging was performed to assist with subsequent tissue resection. Visual findings and semi-quantitative analyses of FACBC and MET uptake, using standardized uptake values (SUVs) and lesion-to-contralateral normal brain tissue (LN) ratios, were evaluated to compare PET images.

Results: SUVs for FACBC were lower than those for MET in the non-lesion cerebral cortex, brain stem, and cerebellar hemisphere. There was a weak positive correlation between FACBC and MET uptake in glioma tissue, although L/N ratios for FACBC were higher than those for MET in all the cases.

Conclusion: FACBC-PET showed higher contrast than MET-PET by both visual and semi-quantitative analyses and may therefore provide better assessment for the detection of glioma. This study was registered as clinical trial (No. JapicCTI-132289).

Keywords: 11C-Methionine; 18F-Fluciclovine; Glioma; Positron emission tomography.

Figures

Figure 1
Figure 1
Manual ROIs in contralateral normal brain Fr: frontal lobe, P parietal lobe, T: temporal lobe, O: occipital lobe, B: basal ganglion, Th: thalamus, C: cerebellar cortex, Po: pons, W: white matter of corona radiata
Figure 2
Figure 2
Comparison between FACBC and MET SUVmean in each normal region SUVmean of FACBC is lower than that of MET in each ROI. F: FACBC-PET, M: MET-PET Fr: frontal lobe, P parietal lobe, T: temporal lobe, O: occipital lobe, B: basal ganglion, Th: thalamus, C: cerebellar cortex, Po: pons, W: white matter of corona radiate
Figure 3
Figure 3
Comparison between FACBC and MET for SUVmean, SUVmax, LNmean, and LNmax in the six cases. SUVmean and SUVmax of FACBC are slightly lower than those of MET (Figures 3A and 3B) with no statistically significant differences. LNmean and LNmax of FACBC are significantly higher than those of MET (Figure 3C and 3D).
Figure 4. Case 1
Figure 4. Case 1
A: Gd contrast-enhanced T1-weighted image B: FLAIR (fluid-attenuated inversion recovery) image C: [11C]methionine positron emission tomography (MET-PET) D: anti- [18F]FACBC positron emission tomography (FACBC-PET) A 40-year-old lady who had poor enhancement homogenous shaped mass in the left frontal lobe in Gd T1-weighted image, which was diagnosed with diffuse astrocytoma, grade II, IDH mutant. FLAIR image showed the high signal lesion around the tumor which had no uptake in FACBC-PET and unclear uptake in MET-PET, and the lesion was diagnosed with edema. High uptake of MET was seen in small part of the tumor, while slight uptake of FACBC was detected against low uptake of background.
Figure 4. Case 2
Figure 4. Case 2
A: Gd contrast-enhanced T1-weighted image B: FLAIR (fluid-attenuated inversion recovery) image C: [11C]methionine positron emission tomography (MET-PET) D: anti- [18F]FACBC positron emission tomography (FACBC-PET) A 61-year-old man who had a diffuse irregular high signal lesion in the left frontal lobe in FLAIR image without enhancement in Gd T1-weighted image. The lesion was diagnosed with diffuse astrocytoma, grade II, IDH mutant. Slight uptake of MET and FACBC was detected in the lesion, but it was difficult to confirm the tumor border in both tracers.
Figure 4. Case 3
Figure 4. Case 3
A: Gd contrast-enhanced T1-weighted image B: FLAIR (fluid-attenuated inversion recovery) image C: [11C]methionine positron emission tomography (MET-PET) D: anti- [18F]FACBC positron emission tomography (FACBC-PET) In a 21-year-old man, the lesion was confirmed as a diffuse low signal lesion without enhancement in Gd T1-weighted image and a slight high irregular lesion in FLAIR image on the left insula lobe. The lesion was diffuse astrocytoma, grade II, IDH mutant. MET-PET showed low uptake in the lesion as well as background. On the other hand, FACBC-PET showed low uptake in the lesion, but slight accumulation was found in small part of the tumor.
Figure 4. Case 4
Figure 4. Case 4
A: Gd contrast-enhanced T1-weighted image B: FLAIR (fluid-attenuated inversion recovery) image C: [11C]methionine positron emission tomography (MET-PET) D: anti- [18F]FACBC positron emission tomography (FACBC-PET) A 57-year-old man who had a small round-shaped mass without enhancement in the right frontal lobe in Gd T1-weighted image, which was diagnosed with oligodendroglioma, grade II, IDH mutant, 1p/19q co-deletion. This case showed 1p19q co-deletion. Both PET tracers were detected in a high signal lesion of FLAIR image, and it was easy to detect the border between tumor and cortex. FACBC-PET showed clearer contrast of abnormal lesion than MET-PET.
Figure 4. Case 5
Figure 4. Case 5
A: Gd contrast-enhanced T1-weighted image B: FLAIR (fluid-attenuated inversion recovery) image C: [11C]methionine positron emission tomography (MET-PET) D: anti- [18F]FACBC positron emission tomography (FACBC-PET) A 70-year-old lady had a slight irregular round-shaped mass in the left frontal lobe. Gd T1-weighted image showed a slight enhancement into the high signal area in FLAIR image. The lesion was diagnosed with anaplastic astrocytoma, IDH wild-type. Though high uptake of MET and FACBC was found in the tumor, FACBC detected more clearly the tumor border than MET. The slight high signal lesion in FLAIR was considered to be edema.
Figure 4. Case 6
Figure 4. Case 6
A: Gd contrast-enhanced T1-weighted image B: FLAIR (fluid-attenuated inversion recovery) image C: [11C]methionine positron emission tomography (MET-PET) D: anti- [18F]FACBC positron emission tomography (FACBC-PET) A 43-year-old man had well-enhanced irregular mass in the corpus callosum of the left frontal lobe in Gd T1-weighted image. The lesion invaded bilateral frontal lobes in FLAIR image. The diagnosis was glioblastoma, IDH mutant. Both MET and FACBC-PET showed high uptake in the tumor and wider area than enhancement lesion in Gd T1-weighted image and smaller than high signal lesion in FLAIR image. A clear margined tumor was depicted in FACBC-PET.

References

    1. Torii K, Tsuyuguchi N, Kawabe J, Sunada I, Hara M, Shiomi S. Correlation of amino-acid uptake using methionine PET and histological classifications in various gliomas. Ann Nucl Med. 2005;19(8):677–83.
    1. 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(6):1640–7.
    1. Nariai T, Tanaka Y, Wakimoto H, Aoyagi M, Tamaki M, Ishiwata K, et al. Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma. J Neurosurg. 2005;103(3):498–507.
    1. Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med. 2008;49(5):694–9.
    1. Takano K, Kinoshita M, Arita H, Okita Y, Chiba Y, Kagawa N, et al. Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas. AJNR Am J Neuroradiol. 2016;37(1):44–50.
    1. Watanabe A, Muragaki Y, Maruyama T, Shinoda J, Okada Y. Usefulness of ¹¹C-methionine positron emission tomography for treatment-decision making in cases of non-enhancing glioma-like brain lesions. J Neurooncol. 2016;126(3):577–83.
    1. Uda T, Tsuyuguchi N, Terakawa Y, Takami T, Ohata K. Evaluation of the accumulation of (11)C-methionine with standardized uptake value in the normal brain. J Nucl Med. 2010;51(2):219–22.
    1. Wakabayashi T, Iuchi T, Tsuyuguchi N, Nishikawa R, Arakawa Y, Sasayama T, et al. Diagnostic performance and safety of positron emission tomography using 18F-fluciclovine in patients with clinically suspected high- or low-grade gliomas:a multicenter phase IIb trial. Asia Ocean J Nucl Med Biol. 2017;5(1):10–21.
    1. Kondo A, Ishii H, Aoki S, Suzuki M, Nagasawa H, Kubota K, et al. Phase IIa clinical study of [18F]fluciclovine:efficacy and safety of a new PET tracer for brain tumors. Ann Nucl Med. 2016;30(9):608–18.
    1. McConathy J, Voll RJ, Yu W, Crowe RJ, Goodman MM. Improved synthesis of anti- [18F]FACBC:improved preparation of labeling precursor and automated radiosynthesis. Appl Radiat Isot. 2003;58(6):657–66.
    1. 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 2005. Eur J Nucl Med Mol Imaging. 2005;32(1):39–51.
    1. 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(5):778–85.
    1. Arita H, Yamasaki K, Matsushita Y, Nakamura T, Shimokawa A, Takami H, et al. A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. Acta Neuropathol Commun. 2016;4(1):79.
    1. Ono M, Oka S, Okudaira H, Schuster DM, Goodman MM, Kawai K, et al. Comparative evaluation of transport mechanisms of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid and L-[methyl-¹¹C]methionine in human glioma cell lines. Brain Res. 2013;1535:24–37.
    1. Okudaira H, Nakanishi T, Oka S, Kobayashi M, Tamagami H, Schuster DM, et al. Kinetic analyses of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2. Nucl Med Biol. 2013;40(5):670–5.
    1. Oka S, Okudaira H, Yoshida Y, Schuster DM, Goodman MM, Shirakami Y. Transport mechanisms of trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid in prostate cancer cells. Nucl Med Biol. 2012;39(1):109–19.
    1. Okudaira H, Shikano N, Nishii R, Miyagi T, Yoshimoto M, Kobayashi M, et al. Putative transport mechanism and intracellular fate of trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid in human prostate cancer. J Nucl Med. 2011;52(5):822–9.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe