比较用于前列腺癌诊断的临床转化研究中的前列腺特异性膜抗原配体。
Comparison of prostate-specific membrane antigen ligands in clinical translation research for diagnosis of prostate cancer.
机构信息
Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology Indore, Indore, India.
Discipline of Biosciences and Biomedical Engineering, School of Engineering, Indian Institute of Technology Indore, Indore, India.
出版信息
Cancer Rep (Hoboken). 2019 Aug;2(4):e1169. doi: 10.1002/cnr2.1169. Epub 2019 Apr 2.
BACKGROUND
Prostate-specific membrane antigen (PSMA), overexpressed on prostate cancer (PCa), is a well-characterized cell surface protein to selectively diagnose PCa. PSMA's unique characteristics and its 1000-fold higher expression in PCa compared with other tissues renders it as a suitable biomarker for detection of PCa in its early stage. In this report, we critically analyze and recommend the requirements needed for the development of variety of PSMA-targeted molecular imaging agents based on antibodies, small molecule ligands, peptides, and aptamers. The targeting moieties are either conjugated to radionuclear isotopes or near-infrared agents for efficient diagnosis of PCa.
RECENT FINDINGS
From the analysis, it was found that several small molecule-derived PCa imaging agents are approved for clinical trials in Europe and the United States, and few are already in the clinical use for diagnosis of PCa. Even though In-labeled capromab pendetide was approved by the Food and Drug Administration (FDA) and other engineered antibodies are available for detection of PCa, but high production cost, low shelf life (less than 1 month at 4°C), possibility of human immuno reactions, and low blood clearance rate necessitated a need for developing new imaging agents, which are serum stable, cost-effective, and possesses longer shelf life (6 months), have fast clearance rate from nontargeted tissues during the diagnosis process. It is found that small molecule ligand-derived imaging agents possesses most of the desired properties expected for an ideal diagnostic agent when compared with other targeting moieties.
CONCLUSION
This report discusses in detail the homing moieties used in the development of targeted diagnostic tools for detection of PCa. The merits and demerits of monoclonal antibodies, small molecule ligands, peptides, and aptamers for imaging of PCa and intraoperative guided surgery are extensively analyzed. Among all, urea-based ligands were found to be most successful in preclinical and clinical trials and show a major promise for future commercialization.
背景
前列腺特异性膜抗原（PSMA）在前列腺癌（PCa）中过度表达，是一种经过充分研究的细胞表面蛋白，可用于选择性诊断 PCa。PSMA 的独特特性及其在 PCa 中的表达水平比其他组织高 1000 倍，使其成为早期检测 PCa 的合适生物标志物。在本报告中，我们对基于抗体、小分子配体、肽和适体的各种 PSMA 靶向分子成像剂的开发要求进行了批判性分析和推荐。靶向部分要么与放射性核素或近红外试剂缀合，以有效诊断 PCa。
最近的发现
从分析中发现，几种小分子衍生的 PCa 成像剂已在欧洲和美国获得临床试验批准，少数已在临床上用于诊断 PCa。尽管 In 标记的 capromab pendetide 已获得美国食品和药物管理局（FDA）批准，其他工程化抗体也可用于检测 PCa，但由于生产成本高、保质期短（在 4°C 下不到 1 个月）、可能发生人类免疫反应以及血液清除率低，因此需要开发新的成像剂，这些成像剂具有血清稳定性、成本效益高，且具有更长的保质期（6 个月），在诊断过程中具有更快的从非靶向组织中清除的速度。与其他靶向部分相比，小分子配体衍生的成像剂具有大多数理想诊断剂所需的特性。
结论
本报告详细讨论了用于开发用于检测 PCa 的靶向诊断工具的归巢部分。广泛分析了单克隆抗体、小分子配体、肽和适体用于 PCa 成像和术中引导手术的优缺点。在所有这些中，基于脲的配体在临床前和临床试验中被发现最成功，并为未来的商业化展示出了巨大的潜力。
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