晚期上皮性卵巢癌术前[18F]氟-PEG-叶酸 PET/CT：安全性和可行性研究

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

Nuclear medicine and biology Pub Date : 2024-09-19 DOI:10.1016/j.nucmedbio.2024.108952

Isabeau A. Ciggaar , Lysanne D.A.N. de Muynck , Lioe-Fee de Geus-Oei , Floris H.P. van Velden , Cornelis D. de Kroon , Lenka M. Pereira Arias-Bouda , Wyanne A. Noortman , Els L. van Persijn van Meerten , Petra Dibbets-Schneider , Hendrik J.F. Helmerhorst , Albert D. Windhorst , Alexander L. Vahrmeijer , Inge T.A. Peters , Katja N. Gaarenstroom

{"title":"晚期上皮性卵巢癌术前[18F]氟-PEG-叶酸 PET/CT：安全性和可行性研究","authors":"Isabeau A. Ciggaar , Lysanne D.A.N. de Muynck , Lioe-Fee de Geus-Oei , Floris H.P. van Velden , Cornelis D. de Kroon , Lenka M. Pereira Arias-Bouda , Wyanne A. Noortman , Els L. van Persijn van Meerten , Petra Dibbets-Schneider , Hendrik J.F. Helmerhorst , Albert D. Windhorst , Alexander L. Vahrmeijer , Inge T.A. Peters , Katja N. Gaarenstroom","doi":"10.1016/j.nucmedbio.2024.108952","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>The selection for either primary or interval cytoreductive surgery (CRS) in patients with epithelial ovarian cancer (EOC) is currently based on imaging techniques like computed tomography (CT), [<sup>18</sup>F]fluorodeoxyglucose-positron emission tomography ([<sup>18</sup>F]FDG-PET), diffusion-weighted magnetic resonance imaging (DW-MRI) and/or diagnostic laparoscopy, but these have limitations. Folate receptor (FR)-targeted PET/CT imaging, using [<sup>18</sup>F]fluoro-PEG-folate, could improve preoperative assessment, potentially reducing unnecessary laparotomies. This paper presents the first experience with [<sup>18</sup>F]fluoro-PEG-folate PET/CT imaging in advanced stage EOC, focusing on safety, tolerability, and feasibility for reflecting the extent of disease.</div></div><div><h3>Methods</h3><div>Tolerability and safety were monitored after administration of the [<sup>18</sup>F]fluoro-PEG-folate tracer by measurements of vital function parameters (blood pressure, heart rate, peripheral oxygen saturation, respiratory rate, and temperature). In addition, (serious) adverse events were recorded. Disease burden was quantified using the Peritoneal Cancer Index (PCI) score on preoperative [<sup>18</sup>F]fluoro-PEG-folate PET/CT and during surgery. PCI scores were compared with intraoperative findings, considering histopathologic results as the gold standard. Tissue specimens were stained for FRα and FRβ. Relative uptake of the radiotracer by EOC lesions and other tissues was quantified using body weighted standardized uptake values (SUV).</div></div><div><h3>Results</h3><div>The study was terminated prematurely during the interim analysis after inclusion of eight patients of whom five had completed the study protocol. Although [<sup>18</sup>F]fluoro-PEG-folate demonstrated safety, efficacy for tumor-specific imaging was limited. Despite clear FRα overexpression, low tracer uptake was observed in EOC lesions, contrasting with high uptake in healthy tissues, posing challenges in specificity and accurately assessing tumor burden.</div></div><div><h3>Conclusions</h3><div>Overall, while [<sup>18</sup>F]fluoro-PEG-folate was well-tolerated, its clinical utility in the preoperative assessment of the extent of disease in EOC was limited. This highlights the need for further research in developing targeted imaging agents for optimal detection of EOC metastases.</div><div>Trial registration: <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span>, NCT05215496. Registered 31 January 2022.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108952"},"PeriodicalIF":3.6000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Preoperative [18F]fluoro-PEG-folate PET/CT in advanced stage epithelial ovarian cancer: A safety and feasibility study\",\"authors\":\"Isabeau A. Ciggaar , Lysanne D.A.N. de Muynck , Lioe-Fee de Geus-Oei , Floris H.P. van Velden , Cornelis D. de Kroon , Lenka M. Pereira Arias-Bouda , Wyanne A. Noortman , Els L. van Persijn van Meerten , Petra Dibbets-Schneider , Hendrik J.F. Helmerhorst , Albert D. Windhorst , Alexander L. Vahrmeijer , Inge T.A. Peters , Katja N. Gaarenstroom\",\"doi\":\"10.1016/j.nucmedbio.2024.108952\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>The selection for either primary or interval cytoreductive surgery (CRS) in patients with epithelial ovarian cancer (EOC) is currently based on imaging techniques like computed tomography (CT), [<sup>18</sup>F]fluorodeoxyglucose-positron emission tomography ([<sup>18</sup>F]FDG-PET), diffusion-weighted magnetic resonance imaging (DW-MRI) and/or diagnostic laparoscopy, but these have limitations. Folate receptor (FR)-targeted PET/CT imaging, using [<sup>18</sup>F]fluoro-PEG-folate, could improve preoperative assessment, potentially reducing unnecessary laparotomies. This paper presents the first experience with [<sup>18</sup>F]fluoro-PEG-folate PET/CT imaging in advanced stage EOC, focusing on safety, tolerability, and feasibility for reflecting the extent of disease.</div></div><div><h3>Methods</h3><div>Tolerability and safety were monitored after administration of the [<sup>18</sup>F]fluoro-PEG-folate tracer by measurements of vital function parameters (blood pressure, heart rate, peripheral oxygen saturation, respiratory rate, and temperature). In addition, (serious) adverse events were recorded. Disease burden was quantified using the Peritoneal Cancer Index (PCI) score on preoperative [<sup>18</sup>F]fluoro-PEG-folate PET/CT and during surgery. PCI scores were compared with intraoperative findings, considering histopathologic results as the gold standard. Tissue specimens were stained for FRα and FRβ. Relative uptake of the radiotracer by EOC lesions and other tissues was quantified using body weighted standardized uptake values (SUV).</div></div><div><h3>Results</h3><div>The study was terminated prematurely during the interim analysis after inclusion of eight patients of whom five had completed the study protocol. Although [<sup>18</sup>F]fluoro-PEG-folate demonstrated safety, efficacy for tumor-specific imaging was limited. Despite clear FRα overexpression, low tracer uptake was observed in EOC lesions, contrasting with high uptake in healthy tissues, posing challenges in specificity and accurately assessing tumor burden.</div></div><div><h3>Conclusions</h3><div>Overall, while [<sup>18</sup>F]fluoro-PEG-folate was well-tolerated, its clinical utility in the preoperative assessment of the extent of disease in EOC was limited. This highlights the need for further research in developing targeted imaging agents for optimal detection of EOC metastases.</div><div>Trial registration: <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span>, NCT05215496. Registered 31 January 2022.</div></div>\",\"PeriodicalId\":19363,\"journal\":{\"name\":\"Nuclear medicine and biology\",\"volume\":\"138 \",\"pages\":\"Article 108952\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-09-19\",\"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/S0969805124000787\",\"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/S0969805124000787","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

目的目前，对上皮性卵巢癌（EOC）患者进行初次或间歇性细胞切除手术（CRS）的选择主要基于计算机断层扫描（CT）、[18F]氟脱氧葡萄糖正电子发射断层扫描（[18F]FDG-PET）、弥散加权磁共振成像（DW-MRI）和/或诊断性腹腔镜检查等成像技术，但这些技术都有局限性。使用[18F]氟-PEG-叶酸的叶酸受体（FR）靶向 PET/CT 成像可改善术前评估，从而减少不必要的开腹手术。本文介绍了[18F]氟-PEG-叶酸 PET/CT 成像在晚期 EOC 中的首次应用经验，重点关注安全性、耐受性和反映疾病程度的可行性。方法在使用[18F]氟-PEG-叶酸示踪剂后，通过测量生命功能参数（血压、心率、外周血氧饱和度、呼吸频率和体温）来监测耐受性和安全性。此外，还记录了（严重）不良事件。在术前[18F]氟-PEG-叶酸 PET/CT 和手术期间，使用腹膜癌指数（PCI）评分对疾病负担进行量化。将 PCI 评分与术中结果进行比较，并将组织病理学结果作为金标准。对组织标本进行 FRα 和 FRβ 染色。结果这项研究在中期分析期间提前结束，纳入了八名患者，其中五名已完成研究方案。尽管[18F]氟-PEG-叶酸证明了其安全性，但对肿瘤特异性成像的疗效有限。结论总的来说，虽然[18F]氟-PEG-叶酸的耐受性良好，但其在术前评估 EOC 病变程度方面的临床作用有限。这凸显了进一步研究开发靶向成像剂以优化EOC转移灶检测的必要性：试验注册：Clinicaltrials.gov，NCT05215496。注册日期：2022 年 1 月 31 日。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Preoperative [18F]fluoro-PEG-folate PET/CT in advanced stage epithelial ovarian cancer: A safety and feasibility study

查看原文本刊更多论文

Preoperative [18F]fluoro-PEG-folate PET/CT in advanced stage epithelial ovarian cancer: A safety and feasibility study

Purpose

The selection for either primary or interval cytoreductive surgery (CRS) in patients with epithelial ovarian cancer (EOC) is currently based on imaging techniques like computed tomography (CT), [¹⁸F]fluorodeoxyglucose-positron emission tomography ([¹⁸F]FDG-PET), diffusion-weighted magnetic resonance imaging (DW-MRI) and/or diagnostic laparoscopy, but these have limitations. Folate receptor (FR)-targeted PET/CT imaging, using [¹⁸F]fluoro-PEG-folate, could improve preoperative assessment, potentially reducing unnecessary laparotomies. This paper presents the first experience with [¹⁸F]fluoro-PEG-folate PET/CT imaging in advanced stage EOC, focusing on safety, tolerability, and feasibility for reflecting the extent of disease.

Methods

Tolerability and safety were monitored after administration of the [¹⁸F]fluoro-PEG-folate tracer by measurements of vital function parameters (blood pressure, heart rate, peripheral oxygen saturation, respiratory rate, and temperature). In addition, (serious) adverse events were recorded. Disease burden was quantified using the Peritoneal Cancer Index (PCI) score on preoperative [¹⁸F]fluoro-PEG-folate PET/CT and during surgery. PCI scores were compared with intraoperative findings, considering histopathologic results as the gold standard. Tissue specimens were stained for FRα and FRβ. Relative uptake of the radiotracer by EOC lesions and other tissues was quantified using body weighted standardized uptake values (SUV).

Results

The study was terminated prematurely during the interim analysis after inclusion of eight patients of whom five had completed the study protocol. Although [¹⁸F]fluoro-PEG-folate demonstrated safety, efficacy for tumor-specific imaging was limited. Despite clear FRα overexpression, low tracer uptake was observed in EOC lesions, contrasting with high uptake in healthy tissues, posing challenges in specificity and accurately assessing tumor burden.

Conclusions

Overall, while [¹⁸F]fluoro-PEG-folate was well-tolerated, its clinical utility in the preoperative assessment of the extent of disease in EOC was limited. This highlights the need for further research in developing targeted imaging agents for optimal detection of EOC metastases.

Trial registration: Clinicaltrials.gov, NCT05215496. Registered 31 January 2022.

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.