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

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.

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer

“…However, apart from the canonical competitive inhibitor of system A transport, MeAIB, no pharmacological agent specifically targeting SLC38A2 has been identified so far. Alternatively, SLC38A2 imaging for clinical selection by AA-based positron emission tomography radiotracers is also a promising approach 59 that might inform treatment strategy. In conclusion, this study provides evidence for future investigation of SLC38A2 as a potential target for TNBC breast cancer patients and as a marker for sensitivity to Gln deprivation.…”

An update on PET-based molecular imaging in neuro-oncology: challenges and implementation for a precision medicine approach in cancer care

“…[N-methyl-C-11]-methylaminoisobutyric acid (MeAIB) is a synthetic amino acid transported through system A neutral amino acid transports and is recently used for brain tumors (28). In 2018, Nishii and colleagues (28) studied the ability of MeAIB for noninvasively differentiating high-grade from low-grade gliomas in clinical setting and compared it with the ability of [S-methyl-C-11]-Lmethionine (MET)-PET.…”

The Next Frontier in Health Disparities—A Closer Look at Exploring Sex Differences in Glioma Data and Omics Analysis, from Bench to Bedside and Back

“…Retrospective studies ( Table 1 ) may provide an avenue for more balanced data sets, given that they can include larger numbers of patients than most prospective studies ( Table 1 and Table 2 ). However, many retrospective studies also report on small numbers of patients [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ], wherein women make up roughly a third of the cohort, and larger studies [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ] do not report on separate analyses for men and women to identify potential sex differences. Prospective studies ( Table 2 ) often involve novel interventions and smaller patient numbers.…”