Fuchigami Takeshi
Graduate School of Biomedical Sciences, Nagasaki University.
Yakugaku Zasshi. 2019;139(12):1531-1538. doi: 10.1248/yakushi.19-00158.
Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are powerful molecular imaging methods for examining disease-related factors in the whole body using specific imaging probes. Recently, we tried to develop molecular imaging probes that specifically visualize pathological factors associated with cancers and infectious diseases. Although survivin is highly expressed in several cancers, its expression is undetectable in non-dividing tissues. Thus, we developed several small molecular imaging probes that target survivin. These ligands not only showed high affinity for survivin protein, but also showed consistent cellular accumulation with respect to survivin expression levels, thereby indicating the feasibility of their backbones as scaffolds for tumor-specific imaging agents that target survivin. Prion diseases are fatal neurodegenerative diseases characterized by the deposition of amyloid plaques containing abnormal prion protein aggregates (PrP). Thus, we developed flavonoids, acridines, and benzofurans as PrP-imaging probes. A styrylchromone derivative ([I]SC-OMe) appears to be a particularly promising SPECT radioligand for monitoring prion deposit levels in living brains. Gallium-68 is a positron emitter in clinical PET applications that can be produced by a Ge/Ga generator without a cyclotron. Notably, we developed new adsorbents for Ge by introducing N-methylglucamine groups into the Sephadex series to serve as a hydrophilic polymer matrix. We also demonstrated that generator-eluted Ga-citrate could be used for PET imaging of infectious mouse models. Our polysaccharide-based Ge/Ga generators were shown to be prospectively cost-effective production systems for Ga radiopharmaceuticals. This Review describes the major findings of these three studies and the future prospect of these fields.
正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）是强大的分子成像方法，可使用特定的成像探针在全身检查与疾病相关的因素。最近，我们试图开发能够特异性可视化与癌症和传染病相关的病理因素的分子成像探针。尽管生存素在多种癌症中高表达，但在非分裂组织中检测不到其表达。因此，我们开发了几种靶向生存素的小分子成像探针。这些配体不仅对生存素蛋白表现出高亲和力，而且在生存素表达水平方面显示出一致的细胞积累，从而表明其骨架作为靶向生存素的肿瘤特异性成像剂支架的可行性。朊病毒病是致命的神经退行性疾病，其特征是含有异常朊病毒蛋白聚集体（PrP）的淀粉样斑块沉积。因此，我们开发了黄酮类、吖啶类和苯并呋喃类作为PrP成像探针。一种苯乙烯基色酮衍生物（[I]SC-OMe）似乎是一种特别有前途的SPECT放射性配体，用于监测活脑内的朊病毒沉积水平。镓-68是临床PET应用中的正电子发射体，可通过Ge/Ga发生器生产，无需回旋加速器。值得注意的是，我们通过将N-甲基葡糖胺基团引入葡聚糖系列开发了新型锗吸附剂，用作亲水性聚合物基质。我们还证明了发生器洗脱的柠檬酸镓可用于感染性小鼠模型的PET成像。我们基于多糖的Ge/Ga发生器被证明是镓放射性药物的潜在经济高效生产系统。本综述描述了这三项研究的主要发现以及这些领域的未来前景。
