[18F]BCPP-EF positron emission tomography of rat ovaries for evaluation of mitochondrial function

Background: The ovary is an important female organ not only for pregnancy but also for the regulation of life activities via hormone release. Ovarian function is measured by blood hormone levels, but the hormone level reflects only the ovarian reserve and no other essential ovarian functions, such as nurturing and expelling follicles. Ovarian fibrosis is related to essential ovarian function; however, the existing methods for evaluating fibrosis are invasive. Ovarian fibrosis has been reported to be associated with mitochondrial function. We hypothesized that positron emission tomography (PET) imaging of mitochondria could be a new, non-invasive method for evaluating essential ovarian function. In this study, we investigated the age-related changes in ovarian fibrosis using the mitochondrial complex-I (MC-I) PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluo- roethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF). Results: Aged rats, whose ovary function decline, exhibited a higher uptake of [18F]BCPP-EF in the ovary than young rats, and this high uptake in aged rats was suppressed by mitoquinone, a superoxide scavenger. Increased [18F]BCPP-EF uptake in the ovary was associated with ovarian fibrosis, but not with AMH level which reflects the ovarian reserve. Furthermore, the measurement of MC protein levels showed that the protein levels of MC-I increased with age, whereas those of MC-V decreased. Conclusions: This study demonstrated that [18F]BCPP-EF can detect age-related changes in essential ovarian function evaluated by ovarian fibrosis. Therefore, [18F]BCPP-EF-PET is a useful non-invasive method for evaluating essential ovarian functions and will contribute to basic research on ovarian aging as well as drug discovery targeting ovarian dysfunction.