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Metabolic kinetic modeling of [11C]methionine based on total-body PET in multiple myeloma

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Abstract

Purpose

Multiple myeloma (MM) is a malignant disease characterized by the secretion of monoclonal immunoglobulins and has a high demand for amino acids. [11C]methionine total-body PET is capable of noninvasive dynamic monitoring of radiotracer in vivo, thus providing a way to reveal the dynamic changes of myeloma metabolism. This study aims to analyze the metabolic process of [11C]methionine based on kinetic modeling, and to preliminary reveal its application value in MM.

Methods

Dynamic total-body [11C]methionine PET/CT was conducted with uEXPLORER in 12 subjects (9 MM patients and 3 controls). The tissue time activity curves (TACs) of organs and bone marrows were extracted. Model fitting of TACs was operated using PMOD Kinetic Modeling. After validation by Goodness of fit (GOF), the reversible two-tissue compartment model (2T4k) was used to further analysis. R software was used to analyze the correlation between kinetic parameters and clinical indicators.

Results

The 2T4k has passed the criterion of GOF and was used to fit the data of 0-20 minutes. The [11C]methionine net uptake rate (Ki) was significantly higher in the MM lesions than in the non-myeloma controls (control: 0.040±0.007 mL/g/min, MM: 0.171±0.108 mL/g/min, p=0.009). The Ki values were found to be correlated with M protein levels in MM patients. MM patients with t(4;14) translocations had an elevated k4 value compared with t(4;14) negative patients.

Conclusion

MM lesions have a propensity for uptake of [11C]methionine. The serum levels of M protein are correlated with [11C]methionine uptake rate in myeloma. Metabolic classification based on the k4 value may be a promising strategy for risk stratification in MM.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This work was supported in part by the National Natural Science Foundation of China (Grant No.82102089 and Grant No.82171972), National Key Research and Development Program of China (Grant No. 2020YFA0909000), Hospital Development Center of Shanghai for Research called “Three-year action plan for major clinical research program” (Grant No. SHDC2020CR20708), Construction Project of Shanghai Key Laboratory of Molecular Imaging (Grant No. 18DZ2260400), and Shanghai Municipal Education Commission (Class II Plateau Disciplinary Construction Program of Medical Technology of SUMHS, 2018–2020).

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Author notes

  1. Jiajin Li and Beiwen Ni contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Jiajin Li, Xiaofeng Yu, Cheng Wang, Lianghua Li, Gang Huang, Jianjun Liu & Yumei Chen

  2. Department of Hematology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Beiwen Ni & Jian Hou

  3. Central Research Institute, United Imaging Healthcare Group Co., Ltd, Shanghai, 200032, China

    Yun Zhou & Yue Gu

  4. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China

    Gang Huang

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jiajin Li, Yumei Chen, and Yue Gu. The first draft of the manuscript was written by Jiajin Li and Xiaofeng Yu, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jian Hou, Jianjun Liu or Yumei Chen.

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All procedures performed in studies involving human participants were approved by the Institutional Review Board of Shanghai Jiao Tong University-affiliated Ren Ji Hospital and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not describe any studies with animals performed by any of the authors.

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Li, J., Ni, B., Yu, X. et al. Metabolic kinetic modeling of [11C]methionine based on total-body PET in multiple myeloma. Eur J Nucl Med Mol Imaging 50, 2683–2691 (2023). https://doi.org/10.1007/s00259-023-06219-y

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