Dataset Information

Improving the stability of ¹¹C-labeled L-methionine with ascorbate.

ABSTRACT:

Background

Carbon-11 labeled L-methionine (¹¹C-MET) is a popular tracer used in the clinic for imaging brain tumors with positron emission tomography. However, the stability of ¹¹C-MET in its final formulation is not well documented in literature. Recently, we observed fast degradation of HPLC-purified ¹¹C-MET over time, and systematic investigation was conducted to identify the cause.

Results

In this study, we verified the degraded product as ¹¹C-labeled methionine sulfoxide (¹¹C-METSO). To minimize oxidation, ascorbate (100 ppm) was added to the HPLC eluant, and the resulting HPLC-purified ¹¹C-MET was stable in the final formulation solution without noticeable degradation for up to 1 h after the end of synthesis.

Conclusions

Our data suggest that to minimize degradation, ascorbate can be added to the ¹¹C-MET formulation solution especially if it is not administered into patients soon after the end of synthesis.

SUBMITTER: Woods M

PROVIDER: S-EPMC5824703 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Improving the stability of <sup>11</sup>C-labeled L-methionine with ascorbate.

Woods Michael M Leung Leo L Frantzen Kari K Garrick Jennifer G JG Zhang Zhengxing Z Zhang Chengcheng C English Wade W Wilson Don D Bénard François F Lin Kuo-Shyan KS

EJNMMI radiopharmacy and chemistry 20171004 1

<h4>Background</h4>Carbon-11 labeled L-methionine (<sup>11</sup>C-MET) is a popular tracer used in the clinic for imaging brain tumors with positron emission tomography. However, the stability of <sup>11</sup>C-MET in its final formulation is not well documented in literature. Recently, we observed fast degradation of HPLC-purified <sup>11</sup>C-MET over time, and systematic investigation was conducted to identify the cause.<h4>Results</h4>In this study, we verified the degraded product as <sup ...[more]

PMID: 29503854

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Project description:Astatine-211 (211At) is an alpha emitter applicable to radioimmunotherapy (RIT), a cancer treatment that utilizes radioactive antibodies to target tumors. In the preparation of 211At-labeled monoclonal antibodies (211At-mAbs), the possibility of radionuclide-induced antibody denaturation (radiolysis) is of concern. Our previous study showed that this 211At-induced radiochemical reaction disrupts the cellular binding activity of an astatinated mAb, resulting in attenuation of in vivo antitumor effects, whereas sodium ascorbate (SA), a free radical scavenger, prevents antibody denaturation, contributing to the maintenance of binding and antitumor activity. However, the influence of antibody denaturation on the pharmacokinetics of 211At-mAbs relating to tumor accumulation, blood circulation time, and distribution to normal organs remains unclear. In this study, we use a radioactive anti-human epidermal growth factor receptor 2 (anti-HER2) mAb to demonstrate that an 211At-induced radiochemical reaction disrupts active targeting via an antigen-antibody interaction, whereas SA helps to maintain targeting. In contrast, there was no difference in blood circulation time as well as distribution to normal organs between the stabilized and denatured immunoconjugates, indicating that antibody denaturation may not affect tumor accumulation via passive targeting based on the enhanced permeability and retention effect. In a high-HER2-expressing xenograft model treated with 1 MBq of 211At-anti-HER2 mAbs, SA-dependent maintenance of active targeting contributed to a significantly better response. In treatment with 0.5 or 0.2 MBq, the stabilized radioactive mAb significantly reduced tumor growth compared to the denatured immunoconjugate. Additionally, through a comparison between a stabilized 211At-anti-HER2 mAb and radioactive nontargeted control mAb, we demonstrate that active targeting significantly enhances tumor accumulation of radioactivity and in vivo antitumor effect. In RIT with 211At, active targeting contributes to efficient tumor accumulation of radioactivity, resulting in a potent antitumor effect. SA-dependent protection that successfully maintains tumor targeting will facilitate the clinical application of alpha-RIT.

Project description:Differentiating tumor recurrence or progression from pseudoprogression during surveillance of pediatric high-grade gliomas (PHGGs) using MRI, the primary imaging modality for evaluation of brain tumors, can be challenging. The aim of this study was to evaluate whether 11C-methionine PET, a molecular imaging technique that detects functionally active tumors, is useful for further evaluating MRI changes concerning for tumor recurrence during routine surveillance. Methods : Using 11C-methionine PET during follow-up visits, we evaluated 27 lesions in 26 patients with new or worsening MRI abnormalities for whom tumor recurrence was of concern. We performed quantitative and qualitative assessments of both 11C-methionine PET and MRI data to predict the presence of tumor recurrence. Further, to assess for an association with overall survival (OS), we plotted the time from development of the imaging changes against survival. Results: Qualitative evaluation of 11C-methionine PET achieved 100% sensitivity, 60% specificity, and 93% accuracy to correctly predict the presence of tumors in 27 new or worsening MRI abnormalities. Qualitative MRI evaluation achieved sensitivity ranging from 86% to 95%, specificity ranging from 40% to 60%, and accuracy ranging from 85% to 89%. The interobserver agreement for 11C-methionine PET assessment was 100%, whereas the interobserver agreement was only 50% for MRI (P < 0.01). Quantitative MRI and 11C-methionine PET evaluation using receiver-operating characteristics demonstrated higher specificity (80%) than did qualitative evaluations (40%-60%). Postcontrast enhancement volume, metabolic tumor volume, tumor-to-brain ratio, and presence of tumor as determined by consensus MRI assessment were inversely associated with OS. Conclusion: 11C-methionine PET has slightly higher sensitivity and accuracy for correctly predicting tumor recurrence, with excellent interobserver agreement, than does MRI. Quantitative 11C-methionine PET can also predict OS. These findings suggest that 11C-methionine PET can be useful for further evaluation of MRI changes during surveillance of previously treated PHGGs.

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Dataset Information

Improving the stability of ¹¹C-labeled L-methionine with ascorbate.

Background

Results

Conclusions

Publications

Improving the stability of <sup>11</sup>C-labeled L-methionine with ascorbate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Improving the stability of 11C-labeled L-methionine with ascorbate.

Background

Results

Conclusions

Publications

Improving the stability of <sup>11</sup>C-labeled L-methionine with ascorbate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Improving the stability of ¹¹C-labeled L-methionine with ascorbate.