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: 10226970
• 负责人: Andrei Iagaru
• 金额: --
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10226970
• 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; detection method; 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.

美国癌症协会的数据表明，前列腺癌（PC）是领先的非态性 2018年男性的癌症诊断，估计为164,690例新病例，其第三高 死亡率为29,430例死亡。当前检测PC和评估的测试方法 对局部靶向疗法（例如PSA测量）的反应没有必要的精度 对于进一步的疾病管理至关重要。治疗后，通过PSA测试，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被混淆 治疗效果和重复的系统活检是侵入性的，可能不会彻底采样所有相关的 组织。需要更好的工具来评估立即反应并检测早期复发。 该项目将采用针对性的方法来改进PC的检测，重点是早期发现 可以通过局部靶向疗法进行治疗的疾病部位以及对这些反应的评估 疗法和预测24个月的无进展生存期。 68GA-RM2是一种合成的bombesin受体拮抗剂，靶向胃蛋白释放肽受体 （grpr）。 GRPR在包括PC在内的几种人类肿瘤中高表达。因为他们的低 在BPH和炎症性前列腺组织中的表达，GRPR的成像比电流具有潜在的优势 基于胆碱和乙酸酯的放射性示例。根据我们的经验，68GA-RM2确定了15名男性的所有主要病变 PC安排了根治性前列腺切除术，并且在80名生化男性中的检测率为70％ 复发（平均PSA：8.0 ng/dL）和负常规成像（骨扫描和CT或MRI）。 前列腺特异性膜抗原（PSMA）是一种细胞表面蛋白，在前列腺中显着过表达 与其他表达PSMA的组织相比，癌细胞，例如肾脏，近端小肠或 唾液腺。 PSMA为PC特异性成像提供了绝佳的目标。已经开发了方法 标签PSMA配体具有68GA，使其用于宠物成像。 68GA-PSMA-11 PET可以在两者下检测PC 最初的诊断和生化复发，通过与PSMA的细胞外结构域结合，具有高对比度。 在前列腺本身中更好地定位癌症也可能通过指导图像为目标产生临床影响 活检和患者选择局部靶向治疗。 虽然68GA-RM2和68GA-PSMA-11都可以检测到PC，但由于它们的靶向 不重叠的PC中涉及的不同生物过程。因此，我们将评估68GA-RM2 PET/MRI和68GA-PSMA-111 PET/MRI用于检测PC和评估对局部靶向的响应 治疗以及预测24个月的无进展生存期。