Evaluation of the Accumulation of <sup>11</sup>C-Methionine with Standardized Uptake Value in the Normal Brain

Uda, Takehiro; Tsuyuguchi, Naohiro; Terakawa, Yuzo; Takami, Toshihiro; Ohata, Kenji

doi:10.2967/jnumed.109.068783

Cited by 12 publications

(14 citation statements)

References 12 publications

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“…In general, amino acid metabolism is low in normal brain tissue and high in tumor tissue. According to this difference in 11 C-MET accumulation, 11 C-MET PET can display clear contrast images for lesions. Therefore, 11 C-MET PET would be an informative modality for detecting the boundary between an active lesion and normal brain tissue (6).…”

Section: Discussionmentioning

confidence: 99%

“…11 C-MET uptake is also informative about the malignancy of lesions, as is 18 F-FDG PET (6,7). For younger patients, it is critical to get accurate information about lesions, such as the degree of malignancy and extent of lesions, as early as possible.…”

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confidence: 99%

“…Therefore, it is essential to have an accurate understanding of 11 C-MET PET data. To date, 11 C-MET PET has been interpreted mainly using the lesion-to-normal (L/N) ratio-comparison between 11 C-MET uptake in the lesion and that in the corresponding normal region in the contralateral hemisphere (8)(9)(10). In cases of a highly malignant lesion, it would be relatively easy to point out where the lesion is, but when the disease has low malignancy, it may be difficult because interpretation of the result is semiquantitative.…”

mentioning

confidence: 99%

“…Thus, an absolute index is desirable. Uda et al determined the normal 11 C-MET uptake and extent of variation (11), but there is no report about normal uptake among children. In the current study, we evaluated normal 11 C-MET uptake in persons younger than 20 y.…”

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confidence: 99%

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Examination of ¹¹C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children

Nagata¹,

Tsuyuguchi²,

Uda³

et al. 2011

J Nucl Med

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The aim of this study was to determine the uptake of L-[methyl-11 C]-methionine ( 11 C-MET) in the normal brain of patients younger than 20 y, to facilitate more accurate diagnoses in young patients. Methods: Eighty-two patients were categorized into 4 groups according to their age. They underwent 11 C-MET PET, and a standardized uptake value (SUV) was determined for different brain regions including the frontal lobe, parietal lobe, cerebellum, and brain stem. Results: Compared with all other parts of the brain, the cerebellum had the highest SUV. A tendency for a positive relationship between SUV and age was found in all regions, and a significant relationship with SUV was found in the frontal lobe and cerebellum. Conclusion: The character of SUV in the normal brains of children is different from that of adults, and these normal SUV data will play an important role as a critical reference value.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Examination of ¹¹C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children

Nagata¹,

Tsuyuguchi²,

Uda³

et al. 2011

J Nucl Med

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“…MET-PET is mainly interpreted by comparing MET uptake in the tumor with that in the corresponding normal region in the contralateral hemisphere or frontal lobe and deriving the TNR. Uda et al [24] reported on MET uptake in the normal brain and report that frontal or parietal cortex are more appropriate as reference regions than the cerebellum or brain stem, as they demonstrate low coefficients of variations. This is the reason, the most often used calculation method is the TNR, which compares the uptake in the tumor to that in the contralateral frontal lobe.…”

Section: Introductionmentioning

confidence: 99%

11C-methionine PET/CT findings in benign brain disease

et al. 2017

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diagnostic accuracy, tumor grading, prognosis, assessment of therapeutic response, assessment of tumor extent, biopsy, and radiotherapy planning, while it also valuable for differentiating between tumor recurrence and radiation necrosis in brain metastases. Brain tumor uptake on MET images can be affected by amino acid transport (sodiumindependent L-transporter, LAT1, 2, and 3), MET metabolism, tumor vascular bed-dependent blood flow, microvessel density, and blood-brain barrier (BBB) distribution [1][2][3]. The accumulation of MET through these mechanisms is visualized as tissue uptake on PET images, with MET being incorporated into most brain tumors, including low-grade gliomas. In general, MET uptake is lower in low-grade than in high-grade gliomas, although there is considerable overlap between these two groups, as well as between histological types [4,5]. However, several previous reports have demonstrated MET uptake in lesions associated with benign brain diseases [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Although Ito et al. [6] have already reported on the imaging spectrum and pitfalls of MET-PET/CT in intracranial lesions, in this review we focus on and introduce imaging characteristics of MET uptake in benign brain disease through a literature review. We recommend physician interpretation of imaging findings and disease characteristics for optimal patient management. Benign uptake must be identified to prevent misdiagnosis and unnecessary surgical operations. These pitfalls in MET-PET image interpretation are important not only for nuclear medicine professionals, but also for radiologists. Methods for the assessment of MET-PET imagesMany reports have made visual assessments and semiquantitative evaluations of MET-PET/CT. The visual assessment of MET-PET images is straightforward and easy.Abstract 11 C-methionine (MET) is one of the most commonly used positron emission tomography (PET) tracers for evaluation of malignant brain tumor, with MET-PET being a sensitive technique for visualization of primary and recurrent malignant brain tumors. However, previous reports have demonstrated MET uptake in lesions associated with benign brain diseases. These diseases usually show an increase in MET uptake similar to that of malignant tumors. This pitfall in MET-PET image interpretation is important not only for nuclear medicine professionals, but also for radiologists. In this review, we demonstrate the imaging characteristics of MET uptake in benign brain disease, and recommend physician interpretation of imaging findings and disease characteristics for optimal patient management. Benign uptake must be identified to prevent misdiagnosis and unnecessary surgical operations.

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Mechanistic safety assessment via multi-omic characterisation of systemic pathway perturbations following in vivo MAT2A inhibition

Fogal,

Michopoulos,

Jarnuczak

et al. 2024

Arch Toxicol

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The tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid development of drugs targeting the MAT2A/PRMT5 axis. MAT2A and its liver- and pancreas-specific isoform, MAT1A, generate the universal methyl donor S-adenosylmethionine (SAM) from ATP and methionine. Given the pleiotropic role SAM plays in methylation of diverse substrates, characterising the extent of SAM depletion and downstream perturbations following MAT2A/MAT1A inhibition (MATi) is critical for safety assessment. We have assessed in vivo target engagement and the resultant systemic phenotype using multi-omic tools to characterise response to a MAT2A inhibitor (AZ’9567). We observed significant SAM depletion and extensive methionine accumulation in the plasma, liver, brain and heart of treated rats, providing the first assessment of both global SAM depletion and evidence of hepatic MAT1A target engagement. An integrative analysis of multi-omic data from liver tissue identified broad perturbations in pathways covering one-carbon metabolism, trans-sulfuration and lipid metabolism. We infer that these pathway-wide perturbations represent adaptive responses to SAM depletion and confer a risk of oxidative stress, hepatic steatosis and an associated disturbance in plasma and cellular lipid homeostasis. The alterations also explain the dramatic increase in plasma and tissue methionine, which could be used as a safety and PD biomarker going forward to the clinic.

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Evaluation of the Accumulation of ¹¹C-Methionine with Standardized Uptake Value in the Normal Brain

Cited by 12 publications

References 12 publications

Examination of ¹¹C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children

Examination of ¹¹C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children

11C-methionine PET/CT findings in benign brain disease

Mechanistic safety assessment via multi-omic characterisation of systemic pathway perturbations following in vivo MAT2A inhibition

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Evaluation of the Accumulation of 11C-Methionine with Standardized Uptake Value in the Normal Brain

Cited by 12 publications

References 12 publications

Examination of 11C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children

Examination of 11C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children

11C-methionine PET/CT findings in benign brain disease

Mechanistic safety assessment via multi-omic characterisation of systemic pathway perturbations following in vivo MAT2A inhibition

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Evaluation of the Accumulation of ¹¹C-Methionine with Standardized Uptake Value in the Normal Brain

Examination of ¹¹C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children

Examination of ¹¹C-Methionine Metabolism by the Standardized Uptake Value in the Normal Brain of Children