THERANOSTICS Center for Molecular Radiotherapy and Precision Oncology, Zentralklinik Bad Berka, Bad Berka, Germany.
Institute for Radiopharmaceutical Chemistry, Technische Universität München, Garching, Germany.
Semin Nucl Med. 2019 Sep;49(5):422-437. doi: 10.1053/j.semnuclmed.2019.06.002. Epub 2019 Jul 6.
Precision oncology is being driven by rapid advances in novel diagnostics and therapeutic interventions, with treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations. Inherent in the theranostics paradigm is the assumption that diagnostic test results can precisely determine whether an individual is likely to benefit from a specific treatment. As part and integral in the current era of precision oncology, theranostics in the context of nuclear medicine aims to identify the appropriate molecular targets in neoplasms (diagnostic tool), so that the optimal ligands and radionuclides (therapeutic tool) with favorable labeling chemistry can be selected for personalized management of a specific disease, taking into consideration the specific patient, and subsequently monitor treatment response. Over the past two decades, the use of gallium-68 labeled peptides for somatostatin receptor (SSTR)-targeted PET/CT (or PET/MRI) imaging followed by lutetium-177 and yttrium-90 labeled SSTR-agonist for peptide receptor radionuclide therapy has demonstrated remarkable success in the management of neuroendocrine neoplasms, and paved the way to other indications of theranostics. Rapid advances are being made in the development of other peptide-based radiopharmaceuticals, small molecular-weight ligands and with newer radioisotopes with more favorable kinetics, potentially useful for theranostics strategies for the clinical application. The present review features the Bad Berka experience with first-in-human studies of new radiopharmaceuticals, for example, prostate-specific membrane antigen ligand, gastrin-releasing peptide receptor, neurotensin receptor 1 ligand, novel SSTR-targeting peptides and nonpeptide, and bone-seeking radiopharmaceuticals. Also new radioisotopes, for example, actinium (Ac), copper (Cu), scandium (Sc), and terbium (Tb/Tb) will be discussed briefly demonstrating the development from basic science to precision oncology in the clinical setting.
精准肿瘤学的发展得益于新型诊断和治疗干预手段的快速进步，这些治疗方法根据个体患者的遗传、生物标志物、表型或社会心理特征进行靶向治疗，这些特征将特定患者与具有相似临床表现的其他患者区分开来。治疗诊断学范式的一个基本假设是，诊断测试结果可以准确确定个体是否可能从特定治疗中受益。作为当前精准肿瘤学时代的一部分，核医学中的治疗诊断旨在确定肿瘤中的适当分子靶标（诊断工具），以便选择具有有利标记化学性质的最佳配体和放射性核素（治疗工具），用于特定疾病的个体化管理，同时考虑到特定患者，并随后监测治疗反应。在过去的二十年中，使用镓-68 标记的肽进行生长抑素受体（SSTR）靶向 PET/CT（或 PET/MRI）成像，然后使用镥-177 和钇-90 标记的 SSTR-激动剂进行肽受体放射性核素治疗，已在神经内分泌肿瘤的治疗管理中取得了显著成功，并为治疗诊断学的其他适应症铺平了道路。其他基于肽的放射性药物、小分子配体和具有更有利动力学的新型放射性同位素的开发也取得了快速进展，这些可能对治疗诊断学策略的临床应用有用。本综述以巴德贝雷克的新放射性药物的人体首次研究经验为特色，例如前列腺特异性膜抗原配体、胃泌素释放肽受体、神经降压素受体 1 配体、新型 SSTR 靶向肽和非肽以及骨靶向放射性药物。还将简要讨论新型放射性同位素，例如锕（Ac）、铜（Cu）、钪（Sc）和铽（Tb/Tb），展示从基础科学到临床环境中的精准肿瘤学的发展。
