Poot Alex J, Lam Marnix G E H, van Noesel Max M
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Department of Solid Tumors, Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.
Front Oncol. 2020 Nov 19;10:578286. doi: 10.3389/fonc.2020.578286. eCollection 2020.
In theranostics (i.e., therapy and diagnostics) radiopharmaceuticals are used for both therapeutic and diagnostic purposes by targeting one specific tumor receptor. Biologically relevant compounds, e.g., receptor ligands or drugs, are labeled with radionuclides to form radiopharmaceuticals. The possible applications are multifold: visualization of biological processes or tumor biology , diagnosis and tumor staging, therapy planning, and treatment of specific tumors. Theranostics research is multidisciplinary and allows for the rapid translation of potential tumor targets from preclinical research to "first-in-man" clinical studies. In the last decade, the use of theranostics has seen an unprecedented value for adult cancer patients. Several radiopharmaceuticals are routinely used in clinical practice (e.g., [Ga/Lu]DOTATATE), and dozens are under (pre)clinical development. In contrast to these successes in adult oncology, theranostics have scarcely been developed to diagnose and treat pediatric cancers. To date, [I]meta-iodobenzylguanidine ([I]mIBG) is the only available and approved theranostic in pediatric oncology. mIBG targets the norepinephrine transporter, expressed by neuroblastoma tumors. For most pediatric tumors, including neuroblastoma, there is a clear need for novel and improved radiopharmaceuticals for imaging and therapy. The strategy of theranostics for pediatric oncology can be divided in (1) the improvement of existing theranostics, (2) the translation of theranostics developed in adult oncology for pediatric purposes, and (3) the development of novel theranostics for pediatric tumor-specific targets. Here, we describe the recent advances in theranostics development in pediatric oncology and shed a light on how this methodology can affect diagnosis and provide additional treatment options for these patients.
在治疗诊断学(即治疗与诊断)中,放射性药物通过靶向一种特定的肿瘤受体用于治疗和诊断目的。生物相关化合物,如受体配体或药物,用放射性核素标记以形成放射性药物。其可能的应用是多方面的:生物过程或肿瘤生物学的可视化、诊断和肿瘤分期、治疗规划以及特定肿瘤的治疗。治疗诊断学研究是多学科的,能够使潜在的肿瘤靶点从临床前研究迅速转化为“首次人体”临床研究。在过去十年中,治疗诊断学对成年癌症患者具有前所未有的价值。几种放射性药物已在临床实践中常规使用(例如,[镓/镥] DOTATATE),还有几十种正处于(临床前)临床开发阶段。与成年肿瘤学的这些成功形成对比的是,治疗诊断学在儿科癌症的诊断和治疗方面几乎没有得到发展。迄今为止,[碘]间碘苄胍([碘] mIBG)是儿科肿瘤学中唯一可用且获批的治疗诊断剂。mIBG靶向神经母细胞瘤肿瘤表达的去甲肾上腺素转运体。对于大多数儿科肿瘤,包括神经母细胞瘤,显然需要新型且改进的放射性药物用于成像和治疗。儿科肿瘤学的治疗诊断学策略可分为:(1)改进现有的治疗诊断剂;(2)将成年肿瘤学中开发的治疗诊断学转化用于儿科目的;(3)开发针对儿科肿瘤特异性靶点的新型治疗诊断剂。在此,我们描述儿科肿瘤学中治疗诊断学发展的最新进展,并阐明这种方法如何影响诊断并为这些患者提供额外的治疗选择。