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

TL;DR

This study explores using [18F]BCPP-BF PET imaging to track mitochondrial dysfunction in a mouse model of kidney disease.

Contribution

The study demonstrates the potential of [18F]BCPP-BF as a non-invasive imaging biomarker for monitoring mitochondrial complex-I in kidney disease.

Findings

[18F]BCPP-BF binding in mouse kidneys decreased by 59–61% after two weeks of adenine treatment.

In vitro autoradiography confirmed a 65.6% reduction in [18F]BCPP-BF specific binding in adenine-fed mice.

The results suggest [18F]BCPP-BF could serve as an imaging biomarker for chronic kidney disease progression.

Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s41181-025-00392-1.

Figures