Prostate Specific Membrane Antigen Targeted Photoacoustic Imaging for Prostate Cancer

前列腺特异性膜抗原靶向光声成像治疗前列腺癌

• 批准号: 9178205
• 负责人: Emad M Boctor
• 金额: $ 22.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9178205
• 关键词: Affinity; Antigen Targeting; Binding; Biological Assay; Cancer Etiology; Cells; Cessation of life; Clinic; Contrast Media; Data; Development; Disease Progression; Drug Kinetics; Dyes; Evaluation; FOLH1 gene; Goals; Hybrids; Image; Imaging Techniques; In Vitro; Integral Membrane Protein; Laboratories; Lasers; Learning; Ligands; Light; Malignant Neoplasms; Malignant neoplasm of prostate; Molecular; Molecular Weight; Monitor; Mus; New Agents; Normal Cell; Optics; PC3 cell line; Penetration; Population; Positron-Emission Tomography; Prostate; Proteins; Radionuclide Imaging; Reporting; Resolution; Series; Signal Transduction; Specificity; Surface of the Prostate; System; Testing; Time; Ultrasonography; abstracting; antigen binding; base; bioimaging; cancer diagnosis; cancer imaging; cancer therapy; design; diffraction of light; experience; flu; fluorescence imaging; imaging agent; imaging modality; imaging system; improved; in vivo; light scattering; men; millimeter; novel; optical imaging; photoacoustic imaging; prostate cancer cell; radiotracer; single photon emission computed tomography; targeted agent; targeted imaging; tumor; uptake; Affinity; Antigen Targeting; Binding; Biological Assay; Cancer Etiology; Cells; Cessation of life; Clinic; Contrast Media; Data; Development; Disease Progression; Drug Kinetics; Dyes; Evaluation; FOLH1 gene; Goals; Hybrids; Image; Imaging Techniques; In Vitro; Integral Membrane Protein; Laboratories; Lasers; Learning; Ligands; Light; Malignant Neoplasms; Malignant neoplasm of prostate; Molecular; Molecular Weight; Monitor; Mus; New Agents; Normal Cell; Optics; PC3 cell line; Penetration; Population; Positron-Emission Tomography; Prostate; Proteins; Radionuclide Imaging; Reporting; Resolution; Series; Signal Transduction; Specificity; Surface of the Prostate; System; Testing; Time; Ultrasonography; abstracting; antigen binding; base; bioimaging; cancer diagnosis; cancer imaging; cancer therapy; design; diffraction of light; experience; flu; fluorescence imaging; imaging agent; imaging modality; imaging system; improved; in vivo; light scattering; men; millimeter; novel; optical imaging; photoacoustic imaging; prostate cancer cell; radiotracer; single photon emission computed tomography; targeted agent; targeted imaging; tumor; uptake

Project Abstract Prostate cancer is one of the leading cancers in the U.S. population and the second leading cause of cancer death in men. Accurate prostate imaging could significantly improve accuracy of the prostate cancer diagnoses and disease progression assessments. Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein that is abundantly expressed on the surface of prostate cancer cells. There are up to 1 million PSMA proteins per cell, making it an excellent target for imaging of prostate cancer. Our group has successfully developed a series of PSMA-based novel low molecular weight PET and SPECT agents for prostate cancer radionuclide imaging. Recently, we reported low molecular weight PSMA-based fluorescent imaging agents derived from conjugation of optical dyes with PSMA-binding ligand and those compounds have shown specific PSMA+ tumor uptake in mice. Optical imaging is very sensitive and can provide high contrast for tumor versus normal cells. However, it has limited penetration depth due to the scattering of the light. Photoacoustic (PA) imaging, based on the photoacoustic effect, is a noninvasive and nonionizing hybrid imaging modality that combines the high contrast of optical contrast with high spatial resolution of ultrasound imaging. It is a promising new biomedical imaging technique with great potential for clinic imaging applications. In this proposal, we are going to design, synthesize and evaluate novel PSMA-targeted low molecular weight PA imaging contrast agents for photoacoustic imaging of prostate cancer. As with our radiotracers and other optical agents, these new agents are expected to concentrate selectively within PSMA-expressing tumors, thereby enhancing the targeting specificity of the PA imaging. The ultimate goal of this project is to developing a new prostate cancer imaging method for improve the prostate cancer diagnosis and treatment monitoring.

项目摘要 前列腺癌是美国人群中的主要癌症之一，也是癌症的第二大原因 男人死亡。准确的前列腺成像可以显着提高前列腺癌诊断的准确性 和疾病进展评估。前列腺特异性膜抗原（PSMA）是II型积分 膜蛋白在前列腺癌细胞表面大量表达。最多有100万 每个细胞的PSMA蛋白质，使其成为前列腺癌成像的绝佳靶标。我们的小组成功 开发了一系列基于PSMA的新型低分子重量PET和SPECT剂，用于前列腺癌 放射性核素成像。最近，我们报道了低分子量基于PSMA的荧光成像剂 来自光学染料与psma结合配体的结合和这些化合物的特异性 小鼠的PSMA+肿瘤吸收。光学成像非常敏感，可以为肿瘤提供高对比度 正常细胞。但是，由于光的散射，它的穿透深度有限。光声（PA） 基于光声效应的成像是一种非侵入性和非离子化混合成像方式， 将光学对比度的高对比度与超声成像的高空间分辨率结合在一起。这是一个有前途的 具有巨大潜力用于临床成像应用的新生物医学成像技术。在这个建议中，我们是 去设计，合成和评估新型PSMA靶向的低分子量PA成像对比度 用于前列腺癌的光声成像。与我们的放射性示例和其他光学剂一样，这些新 预计代理将在表达PSMA表达的肿瘤中有选择性地集中精力，从而增强靶向 PA成像的特异性。该项目的最终目标是开发新的前列腺癌成像 改善前列腺癌诊断和治疗监测的方法。