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Background <p>Chronic kidney disease (CKD) poses a significant global health burden with limited effective treatments for its prevention, progression, and associated complications. Mitochondrial dysfunction is recognized as a pivotal factor in the development of kidney diseases, with mitochondrial complex-I (MC-I) playing a crucial role in assessing overall mitochondrial function. Recent advancements in selective MC-I positron emission tomography (PET) radioligands now allow for non-invasive visualization and quantification of renal mitochondrial status in vivo. The aim of the present study was to evaluate the utility of [<sup>18</sup>F]BCPP-BF in the adenine induced tubulointerstitial nephropathy model.</p> Results <p>Binding of the MC-I targeted PET radioligand, [<sup>18</sup>F]BCPP-BF, showed a gradual decline in the kidneys of mice on an adenine-rich diet. [<sup>18</sup>F]BCPP-BF binding decreased by 59–61% compared to baseline after two weeks of adenine treatment. These results of reduced uptake were further confirmed by in vitro autoradiography. In kidneys from adenine-fed mice, [<sup>18</sup>F]BCPP-BF specific binding was reduced by 65.6% compared to control kidney sections.</p> Conclusions <p>Altogether, the findings suggest that [<sup>18</sup>F]BCPP-BF holds potential as an imaging biomarker for renal failure. However, further preclinical studies and validation in human subjects are necessary before it can be established as a reliable indicator for the progression of CKD.</p>

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PET imaging of mitochondrial complex-I in the adenine-induced tubulointerstitial nephropathy mouse model using [18F]BCPP-BF

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月13日

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  • Kenneth Dahl,
  • Peter Johnström,
  • Miklós Toth,
  • Vasco C. Sousa,
  • Charlotte Ericsson,
  • Maria Strömstedt,
  • Tord Inghardt,
  • Miguel A. Cortés González,
  • Anna Reznichenko,
  • Aurelija Jucaite,
  • Zsolt Cselényi,
  • Robert Unwin,
  • Hiroyuki Ohba,
  • Christer Halldin,
  • Benjamin Challis,
  • Hideo Tsukada,
  • Magnus Schou

摘要

Background

Chronic kidney disease (CKD) poses a significant global health burden with limited effective treatments for its prevention, progression, and associated complications. Mitochondrial dysfunction is recognized as a pivotal factor in the development of kidney diseases, with mitochondrial complex-I (MC-I) playing a crucial role in assessing overall mitochondrial function. Recent advancements in selective MC-I positron emission tomography (PET) radioligands now allow for non-invasive visualization and quantification of renal mitochondrial status in vivo. The aim of the present study was to evaluate the utility of [18F]BCPP-BF in the adenine induced tubulointerstitial nephropathy model.

Results

Binding of the MC-I targeted PET radioligand, [18F]BCPP-BF, showed a gradual decline in the kidneys of mice on an adenine-rich diet. [18F]BCPP-BF binding decreased by 59–61% compared to baseline after two weeks of adenine treatment. These results of reduced uptake were further confirmed by in vitro autoradiography. In kidneys from adenine-fed mice, [18F]BCPP-BF specific binding was reduced by 65.6% compared to control kidney sections.

Conclusions

Altogether, the findings suggest that [18F]BCPP-BF holds potential as an imaging biomarker for renal failure. However, further preclinical studies and validation in human subjects are necessary before it can be established as a reliable indicator for the progression of CKD.