Immuno-PET With Anti-PSMA 89Zr-J591 mAb For Molecular Imaging of Prostate Cancer

使用抗 PSMA 89Zr-J591 mAb 进行免疫 PET 进行前列腺癌分子成像

• 批准号: 8599532
• 负责人: Joseph Reginald Osborne
• 金额: $ 18.38万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8599532
• 关键词: Immuno; PET; Anti; PSMA; 89Zr

DESCRIPTION (provided by applicant): Prostate cancer is the most common solid tumor affecting American adult males. While the disease course is well-understood, there are significant opportunities to improve non-invasive molecular imaging in prostate cancer diagnosis, staging, therapy and management. At present there is no specific radiotracer used for positron emission tomography (PET) - the most sensitive molecular imaging modality. Despite extensive experience in prostate cancer radioimmunotherapy (RIT) clinical trials at Weill Cornell Medical Center based on a humanized monoclonal antibody (huJ591), data analysis has been limited by the lack of quantitative imaging. It is only now possible to combine PET sensitivity with mAb specificity (Immuno- PET) in the clinic. We therefore propose to develop Immuno-PET using J591 mAb and 89Zr - an ideal positron (2+) emitter with physical characteristics necessary for antibody imaging - halflife (3.27 days) and positron energy (Emean = 0.395 MeV). Specifically, this research proposal will test the hypothesis that Immuno-PET based on anti-PSMA (prostate specific membrane antigen) mAb, 89Zr-J591 can enhance specificity, assess tumor progression, and monitor the relative efficacy of current Phase II and III clinical RIT trials. Preclinical studies have been designed using PSMA-positive LNCaP human cell line and non-human RM1.PGLS cell lines to measure specific 89Zr-J591 antigen targeting, internalization and biodistribution in tumor-bearing mice. The results of these studies will be compared and contrasted with another investigational radiopharmaceutical 18F labeled MIP-1224, a PSMA inhibitor. MicroPET non-invasive imaging and biodistribution studies will further determine pharmacokinetics and tumor uptake of these two tracers. To underscore the added value of ImmunoPET in RIT trials, serial PET imaging studies will be performed following 2- radiation from 177Lu-J591 mAb in PSMA (+) xenograft and metastatic cancer models. Following 177Lu-J591 RIT, correlative anatomic imaging studies using a small animal 7 Tesla MRI scanner will be performed. The expected outcome of this study is the development of 89Zr-J591 mAb as an advanced prostate cancer- specific PET radiotracer. The results of this study will have a direct impact on current RIT trials based on anti-PSMA mAb cancer therapy as well as other ongoing prostate cancer imaging trials. The long-term goal will be to improve the specificity of metastatic prostate cancer diagnosis, selection of candidates for treatment, and accuracy of therapeutic dose. Ultimately, these changes will improve management of the large population of patients living with advanced prostate disease

描述（由申请人提供）：前列腺癌是影响美国成年男性的最常见的实体瘤。尽管该疾病的病程已得到充分理解，但在前列腺癌诊断，分期，治疗和管理中有很大的机会来改善非侵入性分子成像。目前，尚无用于正电子发射断层扫描（PET）的特异性放射性示踪剂 - 最敏感的分子成像方式。尽管基于人源化的单克隆抗体（HUJ591）的Weill Cornell医疗中心的前列腺癌免疫疗法（RIT）临床试验丰富的经验，但由于缺乏定量成像，数据分析受到限制。直到现在，才有可能在诊所中将PET灵敏度与MAB特异性（免疫PET）相结合。因此，我们建议使用J591 MAB和89ZR开发免疫-PET-理想的正电子（2+）发射极具有抗体成像所需的物理特征 - 半衰期（3.27天）和正电子能量（EMEAN = 0.395 MEV）。具体而言，该研究建议将检验以下假设：基于抗PSMA（前列腺特异性膜抗原）MAB的免疫PET，89ZR-J591可以提高特异性，评估肿瘤进展，并监测当前II期II期和III期临床RIT试验的相对功效。已经使用PSMA阳性LNCAP人细胞系和非人类RM1.PGLS细胞系设计了临床前研究，以测量含有肿瘤的小鼠中特定的89ZR-J591抗原靶向，内在化和生物分布。这些研究的结果将与另一项标记为MIP-1224（PSMA抑制剂）标记的放射性射击18F进行比较并形成鲜明对比。 MicroPET非侵入性成像和生物分布研究将进一步确定这两个示踪剂的药代动力学和肿瘤吸收。为了强调RIT试验中免疫集的附加值，将在PSMA（+）异种移植物和转移性癌症模型中的177LU-J591 MAB 2-辐射后进行连环PET成像研究。在177LU-J591 RIT之后，将进行使用小动物7 Tesla MRI扫描仪的相关解剖成像研究。这项研究的预期结果是将89ZR-J591 MAB作为晚期前列腺癌 - 特异性PET放射性示踪剂的发展。这项研究的结果将对基于抗PSMA MAB癌症治疗以及其他正在进行的前列腺癌成像试验的当前RIT试验产生直接影响。长期目标是提高转移性​​前列腺癌诊断的特异性，治疗候选者的选择以及治疗剂量的准确性。最终，这些变化将改善患有晚期前列腺疾病的大量患者的管理

项目成果

Erratum to: Repeatability of [68Ga]DKFZ11-PSMA PET Scans for Detecting Prostate-specific Membrane Antigen-positive Prostate Cancer.

勘误：用于检测前列腺特异性膜抗原阳性前列腺癌的 [68Ga]DKFZ11-PSMA PET 扫描的重复性。

• DOI: 10.1007/s11307-017-1104-8
• 发表时间: 2017
• 期刊: Molecular imaging and biology
• 影响因子: 3.1
• 作者: Osborne,JosephR;Kalidindi,TejaM;Punzalan,BlesidaJ;Gangangari,Kishore;Spratt,DanielE;Weber,WolfgangA;Larson,StevenM;Pillarsetty,NagaVaraKishore
• 通讯作者: Pillarsetty,NagaVaraKishore

Utility of FDG-PET in clinical neuroendocrine prostate cancer.

• DOI: 10.1002/pros.22831
• 发表时间: 2014-08
• 期刊: PROSTATE
• 影响因子: 2.8
• 作者: Spratt, Daniel E.;Gavane, Somali;Tarlinton, Lisa;Fareedy, Shoaib B.;Doran, Michael G.;Zelefsky, Michael J.;Osborne, Joseph R.
• 通讯作者: Osborne, Joseph R.