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

• 批准号: 10384193
• 负责人: Rachel Catharine Wilson
• 金额: $ 6.56万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384193
• 关键词: Affect; American; Animals; Binding; Clinical; Clinical Trials; Contrast Media; Cyst; Detection; Diagnosis; Disease; Disease Progression; ESR1 gene; Emission-Computed Tomography; Endometriomas; Endometrium; Estradiol; Estradiol Receptors; Estrogen Receptor 2; Estrogens; Etiology; FPS-FES Oncogene; Functional disorder; Growth; Hemorrhage; Hormones; Human; Image; Imaging Device; Individual; Inflammation; Inflammatory; Intention; Irregular Menstruation; Laparoscopic Surgical Procedures; Lesion; Lesion by Stage; Letrozole; Life Cycle Stages; Location; Magnetic Resonance Imaging; Menstrual cycle; Metabolic; Methodology; Methods; Modeling; Monitor; Nature; North Carolina; Operative Surgical Procedures; Ovarian; Pain; Patients; Pelvic cavity structure; Pelvis; Periodicity; Peritoneal; Positron-Emission Tomography; Procedures; Progesterone; Progesterone Receptors; Property; Quality of life; Recurrence; Reporting; Reproductive Medicine; Research; Resolution; Scanning; 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; base; clinical application; clinically translatable; diagnostic tool; disabling symptom; disease diagnosis; endometriosis; hormone therapy; imaging modality; improved; new technology; non-invasive imaging; nonhuman primate; noninvasive diagnosis; novel therapeutics; pre-clinical research; radiotracer; receptor; reproductive; response; subfertility; tool; uptake

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.

项目总结 大约10%的性成熟女性患有子宫内膜异位症。子宫内膜异位症发生在以下情况 子宫最内层是子宫内膜，位于异位。这种疾病可能会使人虚弱， 症状包括痛经、月经不调和不孕不育。根据大小、位置、 扩散、深度和卵巢受累，疾病状态可能有所不同，并被归类为不同的阶段(即I- 轻度、II-轻度、III-中度和IV-重度)。子宫内膜异位症的分期和确诊仅发生在 通过一个探查性的腹腔镜手术。因为对实施和/或经受侵入性攻击犹豫不决 手术后，治疗往往从临床表现延迟四到八年。此外，尽管几十年来 目前，子宫内膜异位症的病因学和病理生理学研究进展甚微。很难识别早期- 分期的子宫内膜异位病变和无法监测疾病的进展可能阻碍了这项研究 强调需要开发一种非侵入性工具来诊断子宫内膜异位症。虽然成像方式存在 确定晚期和深部浸润性子宫内膜异位症[例如，超声(US)和磁成像 磁共振(MRI)]，检测早期小病变的分辨率不明确。因此，前提是 这项建议的目的是确定利用正电子发射断层扫描(PET/CT)的有效性 确定子宫内膜异位症病变。我们将使用针对雌二醇和孕激素受体(ER)的放射性示踪剂 和PGR)作为PET/CT扫描的造影剂。皮损表达较高水平的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型疾病， 雌二醇不仅包括促进自身的受体(即ER)，还包括促进PGR。尽管ER放射性示踪剂16- 18F-氟-17-雌二醇(α-18F-Fluo-17-βestadiol，FES)已被报道用于诊断深部浸润性子宫内膜异位症，如超声和核磁共振， 目前尚不确定FES是否能检测出较小的病变。这可能是由于FeS优先结合到 ERα而不是ERβ。而子宫内膜异位症的某些阶段表现为ERβ升高，如卵巢 在子宫内膜异位症中，ERα/ERβ在盆腔病变中的表达情况尚不清楚。因此，我们将同时使用FES和 PGR靶向放射性示踪剂21-18F-氟尿酰去孕酮(FFNP)不仅可以识别病变，而且还可以 确定每个放射性示踪剂在以下特定目标中随时间监测病变大小的能力。在目标1中， 我们将比较FES和FFNP在中晚期病变中的摄取率。对于目标2，我们将使用Small 和新开发的损伤，以确定每个放射性示踪剂的检测阈值。最后，在目标3中，我们 会消退中晚期病变用来曲唑，一种常见的治疗子宫内膜异位症的方法来确定 FES和FFNP是否能检测到病变大小随时间的变化。总体而言，这项提案旨在发展 一种非侵入性成像工具，用于诊断和监测子宫内膜异位症病变的进展。为了做到这一点，我们 希望通过大幅减少治疗延误，大幅提高患者的生活质量。我们也 希望通过开发一种随着时间推移追踪病变的新技术来推动对子宫内膜异位症的研究。