BCPP compounds, PET probes for early therapeutic evaluations, specifically bind to mitochondrial complex I

Area of Science:

• Biochemistry
• Neuroscience
• Radiochemistry

Background:

• BCPP compounds are PET imaging probes for neurodegenerative diseases.
• ¹⁸F-BCPP-EF detects neuronal damage via MC-I deficiency, but mechanisms are unclear.

Purpose of the Study:

• Investigate BCPP compounds' effects on mitochondrial complex I (MC-I).
• Determine the specificity of BCPP compounds for MC-I.

Main Methods:

• Utilized cardiomyocyte SMP to study BCPP-BF, -EF, and -EM.
• Assessed inhibition of ³H-dihydrorotenone binding to MC-I.
• Measured MC-I proton pumping activity in vitro.

Main Results:

• BCPP compounds demonstrated concentration-dependent inhibition of MC-I.
• Inhibition of both ³H-dihydrorotenone binding and proton pumping activity was observed.
• Results indicate BCPP compounds are selective MC-I inhibitors.

Conclusions:

• BCPP compounds are selective inhibitors of mitochondrial complex I.
• Radiolabeled BCPP compounds are suitable for quantitative MC-I imaging using PET.
• This supports their utility in diagnosing neurodegenerative diseases.