Challenges in Pharmacokinetic Modelling of [18F]fluoro-PEG-folate PET/CT Imaging in Epithelial Ovarian Cancer Patients.

IF 3 4区 医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Molecular Imaging and Biology Pub Date : 2024-08-01 Epub Date: 2024-05-22 DOI:10.1007/s11307-024-01922-0
Thomas Ruytenberg, Isabeau A Ciggaar, Inge T A Peters, Wyanne A Noortman, Petra Dibbets-Schneider, Lysanne D A N de Muynck, Joeri Kuil, Cornelis D de Kroon, Tom J M Molenaar, Hendrik J F Helmerhorst, Lenka M Pereira Arias-Bouda, Alexander L Vahrmeijer, Albert D Windhorst, Floris H P van Velden, Katja N Gaarenstroom, Lioe-Fee de Geus-Oei
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引用次数: 0

Abstract

Purpose: To describe the pharmacokinetic properties of the [18F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).

Procedures: In five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d'Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [18F]fluoro-PEG6-folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.

Results: The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [18F]fluoro-PEG6-folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.

Conclusion: Performing pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.

Abstract Image

上皮性卵巢癌患者[18F]氟-PEG-叶酸 PET/CT 成像药代动力学建模的挑战。
目的:描述[18F]氟-聚乙二醇(PEG)-叶酸放射性示踪剂在晚期上皮性卵巢癌(EOC)患者 PET/CT 成像中的药代动力学特性:对五名晚期卵巢癌(FIGO IIIB/IIIC 期,国际妇产科联合会)患者静脉注射 185 MBq [18F]fluoro-PEG6-folate 后,直接对盆腔进行 90 分钟动态 PET 采集。在 19 个时间点采集的动脉血样本用于确定血浆输入功能。在 PET 图像上手动绘制了包含肿瘤病灶的静态感兴趣体积(VOI)。使用 PMOD 软件进行建模。通过 Akaike 信息准则比较了三种不同模型(一个 1 组织分区模型(1T2k)和两个 2 组织分区模型,即不可逆模型(2T3k)和可逆模型(2T4k))与时间活动曲线的拟合优度:骨盆区域的药代动力学分析比预期的更具挑战性。在 5 名患者的 22 个肿瘤病灶中,只有 4 个适合进行建模。其余的肿瘤病灶由于示踪剂吸收率低、体积小、靠近其他[18F]氟-PEG6-叶酸亲和结构和/或在动态扫描中因腹腔器官运动而移位等原因而不适合建模。来自四个分析肿瘤病灶的数据表明,不可逆的 2T3k 可能最能描述药代动力学。切除后,所有22个病灶的叶酸受体α(FRα)免疫组化染色均呈阳性:结论:在腹部盆腔区域进行药代动力学分析非常具有挑战性。本文简要介绍了在腹部盆腔区域有限大小的病变中,对一种在肠道中具有高度生理蓄积性的示踪剂进行药代动力学分析所面临的挑战和陷阱。
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来源期刊
CiteScore
6.90
自引率
3.20%
发文量
95
审稿时长
3 months
期刊介绍: Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.
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