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B-Glycine as a marker for β cell imaging and β cell mass evaluation

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

β cell mass (BCM) and function are essential to the diagnosis and therapy of diabetes. Diabetic patients serve β cell loss is, and damage of β cells leads to severe insulin deficiency. Our understanding of the role of BCM in diabetes progression is extremely limited by lacking efficient methods to evaluate BCM in vivo. In vitro methods of labeling islets, including loading of contrast reagent or integration of exogenous biomarker, require artificial manipulation on islets, of which the clinical application is limited. Imaging methods targeting endogenous biomarkers may solve the above problems. However, traditional reagents targeting GLP-1R and VAMT2 result in a high background of adjacent tissues, complicating the identification of pancreatic signals. Here, we report a non-invasive and quantitative imaging technique by using radiolabeled glycine mimics ([18F]FBG, a boron-trifluoride derivative of glycine) to assay islet function and monitor BCM changes in living animals.

Methods

Glycine derivatives, FBG, FBSa, 2Me-FBG, 3Me-FBG, were successfully synthesized and labeled with 18F. Specificity of glycine derivatives were characterized by in vitro experiment. PET imaging and biodistribution studies were performed in animal models carring GLYT over-expressed cells. In vivo evaluation of BCM with [18F]FBG were performed in STZ (streptozocin) induced T1D (type 1 diabetes) models.

Results

GLYT responds to excess blood glycine levels and transports glycine into islet cells to maintain the activity of the glycine receptor (GLYR). Best PET imaging condition was 80 min after given a total of 240 ~ 250 nmol imaging reagent (a mixture of [18F]FBG and natural glycine) intravenously. [18F]FBG can detect both endogenous and exogenous islets clearly in vivo. When applied to STZ induced T1D mouse models, total uptake of [18F]FBG in the pancreas exhibited a linear correlation with survival BCM.

Conclusion

[18F]FBG targeting the endogenous glycine transporter (GLYT), which is highly expressed on islet cells, avoiding extra modification on islet cells. Meanwhile the highly restricted expression pattern of GLYT excluded the background in adjacent tissues. This [18F]FBG-based imaging technique provides a non-invasive method to quantify BCM in vivo, implying a new evaluation index for diabetic assessment.

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Funding

This study was funded by the Beijing Municipal Natural Science Foundation (Grant No. Z200018), the National Natural Science Foundation of China (Grant No. 22225603), the Ministry of Science and Technology of the People’s Republic of China (Grant Nos. 2021YFA1601400 and 2017YFA0506300), the National Nature Science Foundation of China (Grant No. U1867209), the Special Foundation of Beijing Municipal Education Commission (Grant No. 3500-12020123), Li Ge-Zhao Ning Life Science Youth Research Foundation (LGZNQN202004) and Changping Laboratory to Z.L. We thank the facility support from the Analytical Instrumentation Center of Peking University.

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Authors and Affiliations

  1. Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Peking University, Beijing, 100871, China

    Yuxiang Han, Hui Liu, Yimin Li & Zhibo Liu

  2. Center for Life Sciences, Peking University–Tsinghua University, Peking University, Beijing, 100871, China

    Zhibo Liu

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  1. Yuxiang Han
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Zhibo Liu conceived the study; Yuxiang Han assisted by Hui Liu, Yimin Li performed most of the experiments; Yuxiang Han, Yimin Li and Zhibo Liu analysed the data. Yuxiang Han and Zhibo Liu wrote the manuscript with input from all authors. All authors discussed the results and commented on the manuscript.

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Han, Y., Liu, H., Li, Y. et al. B-Glycine as a marker for β cell imaging and β cell mass evaluation. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06712-y

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