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Kidney Week

Abstract: FR-PO382

PET Imaging of Renal Mitochondria in Acute and Progressive Kidney Disease Models Using a Novel PET Probe 18F-BCPP-BF

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Saeki, Satoshi, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan
  • Ohba, Hiroyuki, Hamamatsu Photonics K.K., Hamamatsu, Japan
  • Shimada, Takashi, Research and Development Division, Kyowa Hakko Kirin Co. Ltd., Tokyo, Japan
  • Tsukada, Hideo, Hamamatsu Photonics K.K., Hamamatsu, Japan
  • Nagao, Kenji, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan
Background

The kidney is a highly energy-demanding organ and rich in mitochondria. In addition to physiological importance of mitochondria as a powerhouse, mitochondrial dysfunction is often associated with overproduction of ROS, which is believed to play a critical role the pathogenesis of kidney diseases. Nonetheless, only a few studies have reported the renal mitochondrial status in the clinical settings partly due to a paucity of methodologies.
Recently, Ohba et al. developed a novel PET probe 18F-BCPP-BF specifically binding to mitochondrial complex I (MC-I). 18F-BCPP-BF has a favorable pharmacokinetic property for kidney imaging, which enables us to non-invasively visualize and quantitate the amount of MC-I in whole kidneys in vivo (EJNMMI Research 2016; 6: 82).

Methods

In this study, we demonstrated high-resolution animal PET analyses for kidneys in glomerulonephritis and AKI model animals using 18F-BCPP-BF. .

Results

In anti-GBM glomerulonephritis model rats, the uptake level of 18F-BCPP-BF in kidney showed only slight decrease at the acute phase (74% vs. normal control), while it became more remarkable at the later phase (33% vs. normal control). The significant decrease in the PET signal was accompanied with robust reduction of mitochondrial complex proteins including MC-I, demonstrated by Western blotting analysis. The slight change in PET signals at acute phase despite massive protein urea may reflect less damage in tubular epitheliums.
In rat acute renal I/R model, the renal uptake of 18F-BCPP-BF was slightly decreased at 3 hours after reperfusion (75% vs. sham), when kidney function was slightly declined accompanying morphological abnormality of mitochondria in S3 proximal tubular cells though the loss of proximal tubular epithelial cells was still minimal.

Conclusion

The novel PET probe opens up new possibilities for studying pathophysiological meanings of mitochondrial status in kidney disease, which may be applicable to new clinical diagnosis for patients with various types of kidney diseases.