用于评估线粒体功能的大鼠卵巢[18F]BCPP-EF 正电子发射断层扫描。

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2025-01-22 DOI:10.1016/j.nucmedbio.2025.108996

Yuki Tomonari, Hiroyuki Ohba, Hideo Tsukada

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引用次数: 0

摘要

背景：卵巢是一个重要的女性器官，不仅是怀孕的重要器官，而且通过释放激素来调节生命活动。卵巢功能是通过血液激素水平来衡量的，但激素水平只能反映卵巢储备，而不能反映卵巢的其他基本功能，如培育和排出卵泡。卵巢纤维化与卵巢基本功能有关；然而，现有的评估纤维化的方法是侵入性的。据报道，卵巢纤维化与线粒体功能有关。我们假设线粒体的正电子发射断层扫描（PET）成像可能是一种新的、无创的评估卵巢基本功能的方法。在本研究中，我们使用线粒体复合物-1 (mc -1) PET探针，2-叔丁基-4-氯-5-{6-[2-（2-18F-氟乙氧基）-乙氧基]-吡啶-3-基甲氧基}- 2h -吡嗪-3-one （[18F]BCPP-EF）研究卵巢纤维化的年龄相关性变化。结果：卵巢功能下降的老年大鼠卵巢对[18F]BCPP-EF的摄取高于年轻大鼠，而老年大鼠对[18F]BCPP-EF的摄取受到超氧化物清除剂mitoquinone的抑制。卵巢BCPP-EF摄取增加[18F]与卵巢纤维化有关，但与反映卵巢储备的AMH水平无关。此外，MC蛋白水平测定表明，MC- 1蛋白水平随年龄增长而增加，MC- v蛋白水平随年龄增长而下降。结论：本研究表明[18F]BCPP-EF可以检测卵巢纤维化评估的卵巢基本功能的年龄相关变化。因此，[18F]BCPP-EF-PET是一种有用的无创评估卵巢基本功能的方法，将有助于卵巢衰老的基础研究以及针对卵巢功能障碍的药物发现。

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

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[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-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.

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

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.