{"title":"[<sup>18</sup>F]BCPP-EF positron emission tomography of rat ovaries for evaluation of mitochondrial function.","authors":"Yuki Tomonari, Hiroyuki Ohba, Hideo Tsukada","doi":"10.1016/j.nucmedbio.2025.108996","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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-<sup>18</sup>F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([<sup>18</sup>F]BCPP-EF).</p><p><strong>Results: </strong>Aged rats, whose ovary function decline, exhibited a higher uptake of [<sup>18</sup>F]BCPP-EF in the ovary than young rats, and this high uptake in aged rats was suppressed by mitoquinone, a superoxide scavenger. Increased [<sup>18</sup>F]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.</p><p><strong>Conclusions: </strong>This study demonstrated that [<sup>18</sup>F]BCPP-EF can detect age-related changes in essential ovarian function evaluated by ovarian fibrosis. Therefore, [<sup>18</sup>F]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.</p>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142-143 ","pages":"108996"},"PeriodicalIF":3.6000,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nuclear medicine and biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.nucmedbio.2025.108996","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
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Abstract
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-fluoroethoxy)-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.
期刊介绍：
Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized.
These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field.
Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.
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