Differential Diagnosis between Low-Grade and High-Grade Astrocytoma Using System A Amino Acid Transport PET Imaging with C-11-MeAIB: A Comparison Study with C-11-Methionine PET Imaging.

Ryuichi Nishii,Chio Okuyama,Masaaki Takahashi,Maya Arimoto,Toshihiro Munemitsu,Tatsuya Higashi,Hiroshi Yamauchi,Masaaki Saiki,Masato Kobayashi,Keiichi Kawai,Yoshihiko Kishibe,Shigeki Nagamachi,Susumu Miyamoto,Shinya Kagawa,Shigeki Yamada,Masato Hojo,Masahiro Sawada,Yoshiki Arakawa,Toshinori Hirai

doi:10.1155/2018/1292746

Abstract

Introductions [N-methyl-C-11]α-Methylaminoisobutyric acid (MeAIB) is an artificial amino acid radiotracer used for PET study, which is metabolically stable in vivo. In addition, MeAIB is transported by system A neutral amino acid transport, which is observed ubiquitously in all types of mammalian cells. It has already been shown that MeAIB-PET is useful for malignant lymphoma, head and neck cancers, and lung tumors. However, there have been no reports evaluating the usefulness of MeAIB-PET in the diagnosis of brain tumors. The purpose of this study is to investigate the efficacy of system A amino acid transport PET imaging, MeAIB-PET, in clinical brain tumor diagnosis compared to [S-methyl-C-11]-L-methionine (MET)-PET. Methods Thirty-one consecutive patients (male: 16, female: 15), who were suspected of having brain tumors, received both MeAIB-PET and MET-PET within a 2-week interval. All patients were classified into two groups: Group A as a benign group, which included patients who were diagnosed as low-grade astrocytoma, grade II or less, or other low-grade astrocytoma (n=12) and Group B as a malignant group, which included patients who were diagnosed as anaplastic astrocytoma, glioblastoma multiforme (GBM), or recurrent GBM despite prior surgery or chemoradiotherapy (n=19). PET imaging was performed 20 min after the IV injection of MeAIB and MET, respectively. Semiquantitative analyses of MeAIB and MET uptake using SUVmax and tumor-to-contralateral normal brain tissue (T/N) ratio were evaluated to compare these PET images. ROC analyses for the diagnostic accuracy of MeAIB-PET and MET-PET were also calculated. Results In MeAIB-PET imaging, the SUVmax was 1.20 ± 1.29 for the benign group and 2.94 ± 1.22 for the malignant group (p < 0.005), and the T/N ratio was 3.77 ± 2.39 for the benign group and 16.83 ± 2.39 for the malignant group (p < 0.001). In MET-PET, the SUVmax was 3.01 ± 0.94 for the benign group and 4.72 ± 1.61 for the malignant group (p < 0.005), and the T/N ratio was 2.64 ± 1.40 for the benign group and 3.21 ± 1.14 for the malignant group (n.s.). For the analysis using the T/N ratio, there was a significant difference between the benign and malignant groups with MeAIB-PET with p < 0.001. The result of ROC analysis using the T/N ratio indicated a better diagnosis accuracy for MeAIB-PET for brain tumors than MET-PET (p < 0.01). Conclusions MeAIB, a system A amino acid transport-specific radiolabeled agents, could provide better assessments for detecting malignant type brain tumors. In a differential diagnosis between low-grade and high-grade astrocytoma, MeAIB-PET is a useful diagnostic imaging tool, especially in evaluations using the T/N ratio. Clinical trial registration This trial was registered with UMIN000032498.

Highlights

Positron emission tomography (PET) imaging with amino acid analogs has been focused greatly on clinical applications, as it targets increased amino acid transport by tumors [1, 2]
According to final diagnosis after surgery or biopsy, all patients who met the criteria were classified into the following two groups: Group A, which included patients who were diagnosed as low-grade astrocytoma, grade II including a case of recurrent grade II glioma or less, or other low-grade astrocytomas (n 12; ranging from 5 to 46 years, mean age 32.2 ± 10.0 years; seven males and five females); Group B, which included patients who were diagnosed as anaplastic astrocytoma, glioblastoma multiforme (GBM), or recurrent GBM despite prior surgery or chemoradiotherapy (n 19; ranging from 14 to 71 years, mean age 56.7 ± 16.8 years; nine males and ten females)
System A is capable of transporting N-methylated amino acids [23]. e amino acid analog Methylaminoisobutyric acid (MeAIB) was developed as an ideal tracer for in vivo transport measurements, as the compound is nonmetabolizable and concentrated in cells only via system A transport [15, 20]. ere are several reports regarding clinical MeAIB-PET in patients with lymphoma [14], head and neck cancer [16], in addition to our previous study on pulmonary and mediastinal mass lesions [18], and prostate cancer [19]

Summary

Introduction

Positron emission tomography (PET) imaging with amino acid analogs has been focused greatly on clinical applications, as it targets increased amino acid transport by tumors [1, 2]. For detecting brain tumors, PETstudies with amino acid analogs have been developed [3, 4] to overcome the drawbacks of F-18 FDG (FDG) PET, such as physiological uptake by the brain [5, 6]. An essential sulfur amino acid, is necessary for the growth and development of cells, radiolabelled [S-methyl-C-11]-L-methionine (MET), mainly transported by system L amino acid transporters [7, 8], has been clinically used as a tumor-seeking agent for PET imaging for several decades [9]. MET-PET images can visualize the population and activity of amino acid transport and metabolic events inside the body, such as active cell membrane transport, cellular protein synthesis, polyamine synthesis, and trans-methylation reactions [10, 11]. MET-PET shows faint physiological uptake in the brain, strong physiological uptake in the liver and bone marrow, and uptake in certain types of inflammatory changes [12, 13]

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