Das Sudeep, Imlimthan Surachet, Airaksinen Anu J, Sarparanta Mirkka
Department of Chemistry, University of Helsinki, Helsinki, Finland.
Turku PET Centre, Department of Chemistry, University of Turku, Turku, Finland.
Adv Exp Med Biol. 2021;1295:49-76. doi: 10.1007/978-3-030-58174-9_3.
In the recent years, progress in nanotechnology has significantly contributed to the development of novel pharmaceutical formulations to overcome the drawbacks of conventional treatments and improve the therapeutic outcome in many diseases, especially cancer. Nanoparticle vectors have demonstrated the potential to concomitantly deliver diagnostic and therapeutic payloads to diseased tissue. Due to their special physical and chemical properties, the characteristics and function of nanoparticles are tunable based on biological molecular targets and specific desired features (e.g., surface chemistry and diagnostic radioisotope labeling). Within the past decade, several theranostic nanoparticles have been developed as a multifunctional nanosystems which combine the diagnostic and therapeutic functionalities into a single drug delivery platform. Theranostic nanosystems can provide useful information on a real-time systemic distribution of the developed nanosystem and simultaneously transport the therapeutic payload. In general, the diagnostic functionality of theranostic nanoparticles can be achieved through labeling gamma-emitted radioactive isotopes on the surface of nanoparticles which facilitates noninvasive detection using nuclear molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), meanwhile, the therapeutic effect arises from the potent drug released from the nanoparticle. Moreover, some radioisotopes can concurrently emit both gamma radiation and high-energy particles (e.g., alpha, beta, and Auger electrons), prompting the use either alone for radiotheranostics or synergistically with chemotherapy. This chapter provides an overview of the fundamentals of radiochemistry and relevant radiolabeling strategies for theranostic nanosystem development as well as the methods for the preclinical evaluation of radiolabeled nanoparticles. Furthermore, preclinical case studies of recently developed theranostic nanosystems will be highlighted.
近年来，纳米技术的进步极大地推动了新型药物制剂的发展，以克服传统治疗方法的缺点，并改善许多疾病（尤其是癌症）的治疗效果。纳米颗粒载体已显示出将诊断和治疗有效载荷同时递送至患病组织的潜力。由于其特殊的物理和化学性质，纳米颗粒的特性和功能可根据生物分子靶点和特定的期望特征（例如表面化学和诊断放射性同位素标记）进行调节。在过去十年中，已经开发出几种诊疗纳米颗粒作为多功能纳米系统，将诊断和治疗功能整合到单个药物递送平台中。诊疗纳米系统可以提供有关所开发纳米系统实时全身分布的有用信息，并同时运输治疗有效载荷。一般来说，诊疗纳米颗粒的诊断功能可以通过在纳米颗粒表面标记发射伽马射线的放射性同位素来实现，这有助于使用核分子成像技术（如正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT））进行非侵入性检测，同时，治疗效果来自纳米颗粒释放的强效药物。此外，一些放射性同位素可以同时发射伽马射线和高能粒子（例如阿尔法、贝塔和俄歇电子），促使其单独用于放射诊疗或与化疗协同使用。本章概述了放射化学的基本原理以及用于诊疗纳米系统开发的相关放射性标记策略，以及放射性标记纳米颗粒的临床前评估方法。此外，还将重点介绍最近开发的诊疗纳米系统的临床前案例研究。
