Prostate Specific Membrane Antigen Targeted Photoacoustic Imaging for Prostate Cancer

项目摘要 前列腺癌是美国人的主要癌症之一，也是第二大致癌原因 男人的死亡。准确的前列腺癌成像可以显著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)是一种II型 在前列腺癌细胞表面大量表达的膜蛋白。有多达100万只 PSMA蛋白，使其成为前列腺癌成像的极佳靶点。我们的团队已经成功 开发一系列以PSMA为基础的新型低分子PET和SPECT前列腺癌药物 放射性核素成像。最近，我们报道了基于低分子量聚甲基丙烯酸甲酯的荧光显像剂 来源于光学染料与PSMA结合配体的偶联，这些化合物显示出特定的 小鼠对PSMA肿瘤的摄取。光学成像非常敏感，可以提供高对比度的肿瘤与 正常细胞。然而，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电离的混合成像方式， 结合了光学对比度的高对比度和超声成像的高空间分辨率。这是一个很有前途的 具有巨大临床影像应用潜力的生物医学影像新技术。在这项提案中，我们是 新型PSMA靶向低分子PA成像造影剂的设计、合成与评价 用于前列腺癌的光声成像。与我们的放射性示踪剂和其他光学试剂一样，这些新的 药物有望选择性地集中在表达PSMA的肿瘤中，从而增强靶向性。 PA成像的特异性。该项目的最终目标是开发一种新的前列腺癌成像技术。 提高前列腺癌诊疗监测水平的方法。

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.