Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI

使用 68Ga-RM2 PET、68Ga-PSMA-11 PET 和多参数 MRI 对计划接受高剂量率近距离放射治疗的低风险和中风险前列腺癌患者进行评估

• 批准号: 9975748
• 负责人: Andrei Iagaru
• 金额: $ 61.24万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975748
• 关键词: Ablation; Acetates; Aftercare; Age; American Cancer Society; Benign Prostatic Hypertrophy; Binding; Biochemical; Biodistribution; Biological Process; Biopsy; Bombesin Receptor; Brachytherapy; Cell Surface Proteins; Cessation of life; Choline; Clinical; Clinical Research; Data; Detection; Development; Diagnosis; Disease; Disease Management; Early Diagnosis; Effectiveness; Evaluation; Extracellular Domain; FOLH1 gene; Gland; Goals; High-Dose Rate Brachytherapy; Human; Image; Image Guided Biopsy; Indolent; Inflammatory; Kidney; Label; Lesion; Ligands; Local Therapy; Localized Malignant Neoplasm; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Measurement; Methods; Morbidity - disease rate; PSA level; PSA screening; Patient Selection; Patients; Performance; Positron-Emission Tomography; Prediction of Response to Therapy; Primary Lesion; Progression-Free Survivals; Prostate; Prostate Cancer therapy; Prostatectomy; Prostatic Tissue; Radiation; Radiation therapy; Radical Prostatectomy; Radiopharmaceuticals; Recurrence; Residual Tumors; Residual state; Risk; Salivary Glands; Sampling; Schedule; Screening for Prostate Cancer; Site; Small Intestines; Staging; Stains; Techniques; Technology; Testing; Time; Tissue imaging; Tissues; antigen binding; base; bone imaging; cancer diagnosis; clinical practice; clinically significant; diagnostic accuracy; differential expression; experience; follow-up; image guided; imaging agent; improved; instrumentation; male; men; molecular imaging; mortality; overexpression; overtreatment; phase 2 study; prostate biopsy; prostate cancer cell; prostate cancer risk; radiotracer; receptor binding; response; success; targeted imaging; targeted treatment; tool; treatment effect; treatment response; tumor

Data from the American Cancer Society suggests that prostate cancer (PC) is the leading non-cutaneous cancer diagnosis in males in 2018 in the US with 164,690 estimated new cases and has the third highest mortality with 29,430 estimated deaths. Current testing methods for detection of PC and for assessment of response to local targeted therapy such as PSA measurements do not have the necessary precision that is essential for further disease management. After therapy, assessment of success by PSA testing, MRI and biopsy are unreliable because PSA levels are confounded by residual prostate tissue, MRI is confounded by treatment effects, and repeat systematic biopsies are invasive and may not thoroughly sample all relevant tissue. There is a significant need for better tools to assess immediate response and detect early recurrence. This project will take a targeted approach to improving the detection of PC, with a focus on early detection of sites of disease that can be treated with local targeted therapy, as well as on assessment of response to these therapies and prediction of progression-free survival at 24 months. 68Ga-RM2 is a synthetic bombesin receptor antagonist, which targets gastrin-releasing peptide receptors (GRPr). GRPr are highly overexpressed in several human tumors, including PC. Because of their low expression in BPH and inflammatory prostatic tissues, imaging of GRPr has potential advantages over current choline- and acetate-based radiotracers. In our experience, 68Ga-RM2 identified all primary lesions in 15 men with PC scheduled for radical prostatectomy and had a 70% detection rate in 80 men with biochemical recurrence (mean PSA: 8.0 ng/dl) and negative conventional imaging (bone scan and CT or MRI). Prostate-specific membrane antigen (PSMA) is a cell surface protein significantly overexpressed in prostate cancer cells when compared to other PSMA-expressing tissues such as kidney, proximal small intestine or salivary glands. PSMA provides an excellent target for PC-specific imaging. Methods have been developed to label PSMA ligands with 68Ga, enabling their use for PET imaging. 68Ga-PSMA-11 PET can detect PC at both initial diagnosis and biochemical recurrence with high contrast by binding to the extracellular domain of PSMA. Better localization of cancer within the prostate itself may also have a clinical impact by guiding image-targeted biopsy and patient selection for local targeted therapy. While both 68Ga-RM2 and 68Ga-PSMA-11 can detect PC, their biodistribution is distinct due to their targeting of different biological processes involved in PC that do not overlap. Therefore, we will evaluate both 68Ga-RM2 PET/MRI and 68Ga-PSMA-11 PET/MRI for detection of PC and evaluation of response to local targeted therapy, as well as for prediction of progression-free survival at 24 months.

来自美国癌症协会的数据表明，前列腺癌（PC）是主要的非皮肤性疾病。 美国2018年男性癌症诊断估计有164，690例新病例， 估计死亡人数为29，430人。检测PC和评估PC的当前测试方法 对局部靶向治疗（例如PSA测量）的反应没有必要的精确度，即 对于进一步的疾病管理至关重要。治疗后，通过PSA检测、MRI和 活检是不可靠的，因为PSA水平被残留的前列腺组织混淆，MRI被 治疗效果，重复系统活检是侵入性的，可能无法彻底采样所有相关的 组织.非常需要更好的工具来评估即时反应和发现早期复发。 该项目将采取有针对性的方法来改善PC的检测，重点是早期检测 可以用局部靶向治疗治疗的疾病部位，以及对这些部位的反应评估 治疗和预测24个月时的无进展生存期。 68 Ga-RM 2是一种合成的蛙皮素受体拮抗剂，靶向胃泌素释放肽受体 （GRPr）。GRPr在包括PC在内的几种人类肿瘤中高度过表达。由于其低 在BPH和炎症前列腺组织中表达，GRPr成像具有潜在的优势， 胆碱和醋酸盐放射性示踪剂。在我们的经验中，68 Ga-RM 2确定了15例男性的所有原发性病变 在80例生化检查阳性的男性中， 复发（平均PSA：8.0 ng/dl）和阴性常规成像（骨扫描和CT或MRI）。 前列腺特异性膜抗原（PSMA）是一种在前列腺中显著过表达的细胞表面蛋白， 当与其它表达PSMA的组织如肾、近端小肠或结肠相比时， 唾液腺PSMA为PC特异性成像提供了极好的靶点。方法被开发出来以 用68 Ga标记PSMA配体，使其能够用于PET成像。68 Ga-PSMA-11 PET可以在两种情况下检测PC 通过与PSMA的细胞外结构域结合，以高对比度进行初始诊断和生化复发。 更好地定位前列腺内的癌症本身也可能通过引导图像靶向治疗产生临床影响。 活组织检查和选择患者进行局部靶向治疗。 虽然68 Ga-RM 2和68 Ga-PSMA-11都可以检测PC，但由于它们靶向于 PC中涉及的不同生物过程不重叠。因此，我们将评估68 Ga-RM 2 PET/MRI和68 Ga-PSMA-11 PET/MRI用于检测PC和评价局部靶向治疗的反应 治疗，以及预测24个月时的无进展生存期。