使用[18F]F-TZ3108定量成像评估代谢相关脂肪肝疾病进展和低碳水化合物饮食的疗效

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.2025.108997

Zongping Han , Min Yang , Lei Bi , Peizhen Ye , Yongshan Liu , Pengyuan He , Guolong Huang , Hongjun Jin , Jinyu Xia

{"title":"使用[18F]F-TZ3108定量成像评估代谢相关脂肪肝疾病进展和低碳水化合物饮食的疗效","authors":"Zongping Han , Min Yang , Lei Bi , Peizhen Ye , Yongshan Liu , Pengyuan He , Guolong Huang , Hongjun Jin , Jinyu Xia","doi":"10.1016/j.nucmedbio.2025.108997","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>The Sigma-1 receptor (Sig-1R), located in the mitochondrion-associated membranes (MAMs), is an important biomarker for endoplasmic reticulum (ER) stress and plays a crucial role in the advancement of metabolic-associated fatty liver disease (MAFLD). Despite its significance, current methods to monitor MAFLD progression and treatment response are limited. This study aims to address this gap by utilizing [<sup>18</sup>F]F-TZ3108, an effecient tracer targeting Sig-1R, to quantitatively assess MAFLD progression and the efficacy of a low-carbohydrate diet (LCD) as a potential therapeutic intervention.</div></div><div><h3>Methods</h3><div>The C57 BL/6 J mice were fed either a high-fat diet (HFD) or regular diet (CTR) for 12 weeks, and the progression of MAFLD was continuously monitored at 0, 4, 8, 12 weeks via [<sup>18</sup>F]F-TZ3108 positron emission tomography/computed tomography (PET/CT) and ex vivo assessment. After confirming successful induction, LDC intervention was administered in the HFD group for 2 weeks. And relevant post-treatment evaluations were also performed.</div></div><div><h3>Results</h3><div>PET/CT revealed a continuous decline in the hepatic binding potential (BP<sub>ND</sub>) of [<sup>18</sup>F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BP<sub>ND</sub> in the CTR group. This reduction was significant after the 4th week of induction (<em>p</em> < 0.05). Furthermore, following intervention with LCD, there was a significant improvement in BP<sub>ND</sub> (LCD vs HFD, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The results of this study demonstrate that LCD therapy effectively mitigates MAFLD progression. Furthermore, the use of PET imaging with [<sup>18</sup>F]F-TZ3108 provides a reliable, non-invasive method for monitoring the progression and treatment response of MAFLD, offering significant potential for early detection and personalized treatment evaluation.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108997"},"PeriodicalIF":3.6000,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quantitative imaging using [18F]F-TZ3108 to assess metabolic-associated fatty liver disease progression and low-carbohydrate diet efficacy\",\"authors\":\"Zongping Han , Min Yang , Lei Bi , Peizhen Ye , Yongshan Liu , Pengyuan He , Guolong Huang , Hongjun Jin , Jinyu Xia\",\"doi\":\"10.1016/j.nucmedbio.2025.108997\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>The Sigma-1 receptor (Sig-1R), located in the mitochondrion-associated membranes (MAMs), is an important biomarker for endoplasmic reticulum (ER) stress and plays a crucial role in the advancement of metabolic-associated fatty liver disease (MAFLD). Despite its significance, current methods to monitor MAFLD progression and treatment response are limited. This study aims to address this gap by utilizing [<sup>18</sup>F]F-TZ3108, an effecient tracer targeting Sig-1R, to quantitatively assess MAFLD progression and the efficacy of a low-carbohydrate diet (LCD) as a potential therapeutic intervention.</div></div><div><h3>Methods</h3><div>The C57 BL/6 J mice were fed either a high-fat diet (HFD) or regular diet (CTR) for 12 weeks, and the progression of MAFLD was continuously monitored at 0, 4, 8, 12 weeks via [<sup>18</sup>F]F-TZ3108 positron emission tomography/computed tomography (PET/CT) and ex vivo assessment. After confirming successful induction, LDC intervention was administered in the HFD group for 2 weeks. And relevant post-treatment evaluations were also performed.</div></div><div><h3>Results</h3><div>PET/CT revealed a continuous decline in the hepatic binding potential (BP<sub>ND</sub>) of [<sup>18</sup>F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BP<sub>ND</sub> in the CTR group. This reduction was significant after the 4th week of induction (<em>p</em> < 0.05). Furthermore, following intervention with LCD, there was a significant improvement in BP<sub>ND</sub> (LCD vs HFD, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The results of this study demonstrate that LCD therapy effectively mitigates MAFLD progression. Furthermore, the use of PET imaging with [<sup>18</sup>F]F-TZ3108 provides a reliable, non-invasive method for monitoring the progression and treatment response of MAFLD, offering significant potential for early detection and personalized treatment evaluation.</div></div>\",\"PeriodicalId\":19363,\"journal\":{\"name\":\"Nuclear medicine and biology\",\"volume\":\"144 \",\"pages\":\"Article 108997\"},\"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://www.sciencedirect.com/science/article/pii/S096980512500006X\",\"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}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nuclear medicine and biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S096980512500006X","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}

引用次数: 0

摘要

目的Sigma-1受体（Sig-1R）位于线粒体相关膜（MAMs），是内质网（ER）应激的重要生物标志物，在代谢相关脂肪肝（MAFLD）的进展中起着至关重要的作用。尽管具有重要意义，但目前监测mald进展和治疗反应的方法有限。本研究旨在通过利用[18F]F-TZ3108（一种针对Sig-1R的有效示踪剂）来定量评估MAFLD的进展和低碳水化合物饮食（LCD）作为潜在治疗干预措施的疗效来解决这一空白。方法C57 BL/6 J小鼠分别饲喂高脂饮食（HFD）和常规饮食（CTR） 12周，通过[18F]F-TZ3108正电子发射断层扫描/计算机断层扫描（PET/CT）和离体评估，在0、4、8、12周连续监测mald的进展情况。在确认诱导成功后，HFD组进行LDC干预2周。并进行相应的治疗后评价。结果与CTR组相比，HFD组小鼠的肝结合电位（BPND）在诱导期内持续下降。这种减少在诱导第4周后是显著的(p <；0.05)。此外，在LCD干预后，BPND有显著改善（LCD vs HFD, p = 0.001）。结论本研究结果表明LCD治疗可有效缓解MAFLD的进展。此外，使用PET成像[18F]F-TZ3108提供了一种可靠的、无创的方法来监测MAFLD的进展和治疗反应，为早期发现和个性化治疗评估提供了巨大的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Quantitative imaging using [18F]F-TZ3108 to assess metabolic-associated fatty liver disease progression and low-carbohydrate diet efficacy

查看原文本刊更多论文

Quantitative imaging using [18F]F-TZ3108 to assess metabolic-associated fatty liver disease progression and low-carbohydrate diet efficacy

Objective

The Sigma-1 receptor (Sig-1R), located in the mitochondrion-associated membranes (MAMs), is an important biomarker for endoplasmic reticulum (ER) stress and plays a crucial role in the advancement of metabolic-associated fatty liver disease (MAFLD). Despite its significance, current methods to monitor MAFLD progression and treatment response are limited. This study aims to address this gap by utilizing [¹⁸F]F-TZ3108, an effecient tracer targeting Sig-1R, to quantitatively assess MAFLD progression and the efficacy of a low-carbohydrate diet (LCD) as a potential therapeutic intervention.

Methods

The C57 BL/6 J mice were fed either a high-fat diet (HFD) or regular diet (CTR) for 12 weeks, and the progression of MAFLD was continuously monitored at 0, 4, 8, 12 weeks via [¹⁸F]F-TZ3108 positron emission tomography/computed tomography (PET/CT) and ex vivo assessment. After confirming successful induction, LDC intervention was administered in the HFD group for 2 weeks. And relevant post-treatment evaluations were also performed.

Results

PET/CT revealed a continuous decline in the hepatic binding potential (BP_ND) of [¹⁸F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BP_ND in the CTR group. This reduction was significant after the 4th week of induction (p < 0.05). Furthermore, following intervention with LCD, there was a significant improvement in BP_ND (LCD vs HFD, p = 0.001).

Conclusions

The results of this study demonstrate that LCD therapy effectively mitigates MAFLD progression. Furthermore, the use of PET imaging with [¹⁸F]F-TZ3108 provides a reliable, non-invasive method for monitoring the progression and treatment response of MAFLD, offering significant potential for early detection and personalized treatment evaluation.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

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.