Dataset Information

PET Imaging with S-[11C]Methyl-L-Cysteine and L-[Methyl-11C]Methionine in Rat Models of Glioma, Glioma Radiotherapy, and Neuroinflammation.

ABSTRACT: PURPOSE:S-[11C]-methyl-L-cysteine ([11C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl- 11C]methionine ([11C]MET). We examined this claim in animal models. PROCEDURES:Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days. RESULTS:Uptake of the two tracers in untreated gliomas was similar. [11C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [11C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [11C]MCYS indicated higher lesion volumes than [11C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %). CONCLUSIONS:[11C]MCYS was less accumulated in some non-tumor tissues than [11C]MET, but showed lower tumor-to-brain contrast.

SUBMITTER: Parente A

PROVIDER: S-EPMC5938303 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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PET Imaging with S-[<sup>11</sup>C]Methyl-L-Cysteine and L-[Methyl-<sup>11</sup>C]Methionine in Rat Models of Glioma, Glioma Radiotherapy, and Neuroinflammation.

Parente Andrea A van Waarde Aren A Shoji Alexandre A de Paula Faria Daniele D Maas Bram B Zijlma Rolf R Dierckx Rudi A J O RAJO Langendijk Johannes A JA de Vries Erik F J EFJ Doorduin Janine J

Molecular imaging and biology 20180601 3

<h4>Purpose</h4>S-[<sup>11</sup>C]-methyl-L-cysteine ([<sup>11</sup>C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl- <sup>11</sup>C]methionine ([<sup>11</sup>C]MET). We examined this claim in animal models.<h4>Procedures</h4>Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysacch ...[more]

PMID: 29086198

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Project description:Background and purposeNoninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas.Materials and methodsThirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival.ResultsGrade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044).Conclusions(11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.

Project description:PURPOSE:[11C]methionine ([11C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types. However, the short half-life of 11C decay limited further clinical development of [11C]Met. Synthetic amino acid analog anti-1-amino-3-[18F]fluoro-cyclobutyl-1-carboxylic acid ([18F]FCABC) was developed and FDA-approved for PET imaging of recurrent prostate cancer. This study investigated "repurposed" [18F]FACBC for PET imaging of primary liver cancer such as hepatocellular carcinoma (HCC) in comparison with [11C]Met. METHODS:[11C]Met was synthesized in the lab, and [18F]FACBC was purchased from a commercial outlet. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for PET imaging. Bioinformatics analysis was performed for the expression of amino acid transporters responsible for radiotracer uptake and validated by PCR. Dynamic PET scans of [11C]Met and [18F]FACBC were acquired within 1 week. Standardized uptake value (SUV) was calculated for regions of interest (ROIs) defined over HCC and a liver background region. H&E staining and immunohistochemical (IHC) staining were performed with harvested tissues post-imaging. RESULTS:Higher expression of ACST2 and LAT1 was found in HCC than in the surrounding liver tissues. PCR validated this differential expression. [11C]Met and [18F]FACBC displayed some differences in their uptake and retention in HCC. Both peaked in HCC with an SUV of 3.5 after 10 min post-injection. Met maintained a plateaued contrast uptake in HCC to that in the liver while [18F]FCABC declined in HCC and liver after peak uptake. The pathological assessment revealed the liver tumor as moderately differentiated similar to the human HCC and proliferative. CONCLUSION:Both [18F]FACBC and [11C]Met showed uptake in HCC through the use of a clinically relevant animal model of woodchuck HCC. The uptake and retention of [18F]FACBC and [11C]Met depend on their metabolism and also rely on the distribution of their principal amino acid transporters.

Dataset Information

PET Imaging with S-[11C]Methyl-L-Cysteine and L-[Methyl-11C]Methionine in Rat Models of Glioma, Glioma Radiotherapy, and Neuroinflammation.

Publications

PET Imaging with S-[<sup>11</sup>C]Methyl-L-Cysteine and L-[Methyl-<sup>11</sup>C]Methionine in Rat Models of Glioma, Glioma Radiotherapy, and Neuroinflammation.

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