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Evaluation of 18F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

We have reported on the development of a novel PET probe, 18F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (18F-BCPP-EF), for quantitative imaging of mitochondrial complex 1 (MC-1) activity in the brain of the living rat. For clinical application in humans, translational research in the monkey was conducted.

Methods

PET measurements with 18F-BCPP-EF were performed in young and old monkeys (Macaca mulatta) in a conscious state with arterial blood sampling. The binding specificity of 18F-BCPP-EF was evaluated with rotenone, a specific MC-1 inhibitor, in young animals. The binding (total distribution volume, V T) of 18F-BCPP-EF was calculated using Logan graphical analysis, and one-tissue compartment model (1-TC) and two-tissue compartment model (2-TC) analyses using a metabolite-corrected plasma input function.

Results

F-BCPP-EF was rapidly taken up into the brain just after intravenous injection, peaked between 10 and 20 min after injection, and was then gradually eliminated. The 2-TC analysis provided a better fit than the 1-TC analysis, and the V T values from the 2-TC analysis correlated well with those from the Logan plot. With predosing with rotenone, 18F-BCPP-EF showed a higher uptake peak in the brain, followed by more rapid elimination thereafter than in the vehicle condition, resulting in significant reductions in 2-TC V T values in all regions. In old animals, the kinetics of 18F-BCPP-EF were slightly slower with lower peak levels than in young animals, resulting age-related reductions in 18F-BCPP-EF binding in all brain regions.

Conclusion

The present study demonstrated that 18F-BCPP-EF may be a potential PET probe for quantitative imaging MC-1 activity in the living brain using PET.

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Acknowledgments

We gratefully acknowledge the technical assistance provided by Aiko Iwazaki, Shingo Nishiyama, and Shigeyuki Yamamoto.

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Authors and Affiliations

  1. Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, Hamamatsu, Shizuoka, 434-8601, Japan

    Hideo Tsukada, Hiroyuki Ohba, Masakatsu Kanazawa, Takeharu Kakiuchi & Norihiro Harada

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  1. Hideo Tsukada
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  2. Hiroyuki Ohba
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  3. Masakatsu Kanazawa
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  4. Takeharu Kakiuchi
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  5. Norihiro Harada
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Correspondence to Hideo Tsukada.

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Tsukada, H., Ohba, H., Kanazawa, M. et al. Evaluation of 18F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET. Eur J Nucl Med Mol Imaging 41, 755–763 (2014). https://doi.org/10.1007/s00259-013-2628-z

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  • DOI: https://doi.org/10.1007/s00259-013-2628-z

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