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) 是主要的非皮肤癌 2018 年美国男性癌症诊断估计新增病例 164,690 例，位居第三 死亡人数估计为 29,430 人。当前用于检测 PC 和评估 PC 的测试方法 对局部靶向治疗（如 PSA 测量）的反应不具备必要的精确度 对于进一步的疾病管理至关重要。治疗后，通过 PSA 测试、MRI 和 活检不可靠，因为 PSA 水平与残留前列腺组织混淆，MRI 与 治疗效果和重复系统活检是侵入性的，可能无法彻底采样所有相关的样本 组织。迫切需要更好的工具来评估即时反应并检测早期复发。 该项目将采取有针对性的方法来改进PC的检测，重点是早期检测 可以通过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 24 个月无进展生存期预测。 68Ga-RM2 是一种合成的铃蟾肽受体拮抗剂，针对胃泌素释放肽受体 （GRP）。 GRPr 在包括 PC 在内的多种人类肿瘤中高度过表达。由于他们的低 GRPr 在 BPH 和炎症性前列腺组织中表达，GRPr 成像比目前的成像具有潜在优势 基于胆碱和醋酸盐的放射性示踪剂。根据我们的经验，68Ga-RM2 识别出 15 名男性的所有原发性病变 计划进行根治性前列腺切除术的 PC 在 80 名患有生化检查的男性中检出率为 70% 复发（平均 PSA：8.0 ng/dl）和常规影像（骨扫描和 CT 或 MRI）阴性。 前列腺特异性膜抗原（PSMA）是一种在前列腺中显着过度表达的细胞表面蛋白 与其他表达 PSMA 的组织（例如肾脏、近端小肠或 唾液腺。 PSMA 为 PC 特定成像提供了极好的目标。已开发出方法 用 68Ga 标记 PSMA 配体，使其能够用于 PET 成像。 68Ga-PSMA-11 PET 可以同时检测 PC 通过与 PSMA 胞外域结合，以高对比度进行初步诊断和生化复发。 通过引导图像​​靶向，更好地定位前列腺本身的癌症也可能产生临床影响 活检和患者选择以进行局部靶向治疗。 虽然 68Ga-RM2 和 68Ga-PSMA-11 都可以检测 PC，但由于它们的靶向作用，它们的生物分布是不同的 PC 涉及的不同生物过程不重叠。因此，我们将评估这两款 68Ga-RM2 PET/MRI 和 68Ga-PSMA-11 PET/MRI 用于检测 PC 并评估对局部靶向的反应 治疗，以及预测 24 个月无进展生存期。