Monitoring the progression of endometriosis using PET/CT imaging

使用 PET/CT 成像监测子宫内膜异位症的进展

基本信息

批准号：
10583449
负责人：
Rachel Catharine Wilson
金额：
$ 2.03万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10583449
关键词：
Ablation Affect American Animals Binding Classification Clinical Clinical Trials Contrast Media Cyst Detection Diagnosis Disease Disease Progression ESR1 gene Early identification Emission-Computed Tomography Endometriomas Endometrium Estradiol Estradiol Receptors Estrogen Receptor 2 Estrogen Receptor alpha Estrogens Etiology Functional disorder Growth Hemorrhage Hormones Human Image Imaging Device Individual Infiltration Inflammation Inflammatory Intention Irregular Menstruation Laparoscopic Surgical Procedures Lesion Lesion by Stage Letrozole Life Cycle Stages Location Magnetic Resonance Imaging Menstrual cycle Menstruation Metabolic Methodology Methods Modeling Monitor Nature North Carolina Operative Surgical Procedures Ovarian Pain Patients Pelvic cavity structure Pelvis Peritoneal Positron-Emission Tomography Procedures Progesterone Progesterone Receptors Property Quality of life Recurrence Reporting Reproductive Medicine Research Resolution Sensitivity and Specificity Societies Staging Steroid Receptors Symptoms Techniques Therapeutic Therapeutic Intervention Time Tissues Tracer Translational Research Ultrasonography Universities Uterus Woman X-Ray Computed Tomography aged alternative treatment clinical application clinical translation diagnostic tool disease diagnosis efficacy evaluation endometriosis hormone therapy imaging modality improved new technology non-invasive imaging nonhuman primate noninvasive diagnosis novel therapeutics overexpression pre-clinical research radiotracer receptor reproductive response subfertility tool uptake

项目摘要

PROJECT SUMMARY Approximately 10% of sexually mature women are afflicted with endometriosis. Endometriosis occurs when the inner most lining of the uterus, the endometrium, is located ectopically. This disease can be debilitating and symptoms include painful periods, heavy and irregular menstruation, and subfertility. Based on size, location, spread, depth, and ovarian involvement, disease state can vary and is classified as different stages (i.e., I- minimal, II-mild, III-moderate, and IV-severe). Staging and a definitive diagnosis of endometriosis only occur through an exploratory laparoscopic surgery. Because of a hesitancy to perform and/or undergo an invasive surgery, treatment is often delayed four to eight years from clinical presentation. Further, despite decades of research, the etiology and pathophysiology of endometriosis has progressed little. Difficulty in identifying early- stage endometriotic lesions and the inability to monitor disease progression has likely hindered this research highlighting the need to develop a non-invasive tool to diagnosis endometriosis. While imaging modalities exist to identify late stage and deep infiltrating endometriosis [e.g., ultrasonography (US) and magnetic imaging resonance (MRI)], the resolution of detecting small, early stage lesions is equivocal. Therefore, the premise of this proposal is determine the efficacy in utilizing positron emission tomography (PET/CT) to identify endometriotic lesions. We will use radiotracers targeted to estradiol and progesterone receptors (ER and PGR, respectively) as contrast agents for PET/CT scans. Lesions express higher levels of ER and PGR compared to surrounding tissues because endometriosis is an estrogen-dependent disease and actions of estradiol include promoting not only its own receptor (i.e., ER), but also PGR. Although the ER radiotracer 16- α-18F-fluoro-17-β estradiol (FES) has been reported to identify deep infiltrating endometriosis, like US and MRI, it is uncertain whether FES can detect smaller lesions. This is likely due to the preferential binding of FES to ERα rather than ERβ. While some stages of endometriosis display elevated ERβ such as ovarian endometriomas, the ratio of ERα/ERβ in pelvic lesions is unclear. Therefore, we will use both FES and the PGR targeted radiotracer 21-18F-fluorofuranyl-norprogesterone (FFNP) to not only identify lesions, but also to determine each radiotracer’s ability to monitor lesion size over time in the following Specific Aims. In Aim 1, we will compare the uptake rates of FES and FFNP in mid- to late-stage lesions. For Aim 2, we will use small and newly developed lesions to identify the detection thresholds of each radiotracer. And finally, in Aim 3, we will regress mid- to late-stage lesions with letrozole, a common therapeutic for endometriosis to determine whether FES and FFNP can detect changes in lesion size over time. Collectively, this proposal aims to develop a non-invasive imaging tool to diagnosis and monitor the progression of endometriotic lesions. In doing so, we hope to substantially increase patient quality of life by substantially decreasing the delay to treatment. We also hope to drive research on endometriosis forward by developing a new technology to track lesions over time.

项目概要大约 10% 的性成熟女性患有子宫内膜异位症。子宫的最内层，即子宫内膜，位于异位，这种疾病可能会使人衰弱。症状包括经痛、月经量多且不规则，以及生育能力低下。由于扩散、深度和卵巢受累，疾病状态可能会有所不同，并被分为不同的阶段（即 I- 仅发生子宫内膜异位症的分期和明确诊断。由于对执行和/或接受侵入性手术犹豫不决。此外，尽管已经进行了数十年，但治疗通常会从临床表现延迟四到八年。子宫内膜异位症的病因学和病理生理学研究进展甚微。阶段子宫内膜异位病变和无法监测疾病进展可能阻碍了这项研究强调在存在成像方式的情况下开发一种非侵入性工具来诊断子宫内膜异位症的必要性。识别晚期和深层浸润性子宫内膜异位症[例如超声检查（美国）和磁成像磁共振（MRI）]，检测小的早期病变的分辨率是模棱两可的，因此，前提。该提案的目的是确定利用正电子发射断层扫描 (PET/CT) 的功效我们将使用针对雌二醇和孕激素受体（ER）的放射性示踪剂来识别子宫内膜异位病变。和 PGR）作为 PET/CT 扫描的造影剂，病变表达较高水平的 ER 和 PGR。与周围组织相比，因为子宫内膜异位症是一种雌激素依赖性疾病，并且雌二醇不仅包括促进其自身的受体（即ER），还包括PGR，尽管ER放射性示踪剂16-。据报道，α-18F-氟-17-β雌二醇 (FES) 可识别深部浸润性子宫内膜异位症，如超声和 MRI，尚不确定 FES 是否可以检测较小的病变，这可能是由于 FES 优先结合。 ERα 而不是 ERβ，而子宫内膜异位症的某些阶段显示 ERβ 升高，例如卵巢。子宫内膜异位症中，盆腔病变中 ERα/ERβ 的比率尚不清楚，因此，我们将同时使用 FES 和 PGR 靶向放射性示踪剂 21-18F-氟呋喃基-去甲孕酮 (FFNP) 不仅可以识别病变，还可以在以下具体目标 1 中，确定每个放射性示踪剂随着时间的推移监测病变大小的能力。我们将比较中晚期病变中 FES 和 FFNP 的摄取率对于目标 2，我们将使用小型。和新出现的病变来确定每种放射性示踪剂的检测阈值最后，在目标 3 中，我们。将使用来曲唑（子宫内膜异位症的常见治疗方法）来消退中晚期病变，以确定 FES 和 FFNP 是否可以检测病变大小随时间的变化。总的来说，该提案旨在开发。一种用于诊断和监测子宫内膜异位病变进展的非侵入性成像工具。我们还希望通过大幅减少治疗延误来大幅提高患者的生活质量。希望通过开发一种追踪病变时间的新技术来推动子宫内膜异位症的研究向前发展。