Curanosticum Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, D-65191 Wiesbaden, Germany.
Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, D-69120 Heidelberg, Germany.
Molecules. 2022 May 23;27(10):3354. doi: 10.3390/molecules27103354.
The use of immunotherapy has revolutionized the treatment regimen of certain cancer types, but response assessment has become a difficult task with conventional methods such as CT/MRT or FDG PET-CT and the classical response criteria such as RECIST or PERCIST which have been developed for chemotherapeutic treatment. Plenty of new tracers have been published to improve the assessment of treatment response and to stratify the patient population. We gathered the information on published tracers (in total, 106 individual SPECT/PET tracers were identified) and performed a descriptor-based analysis; in this way, we classify the tracers with regard to target choice, developability (probability to progress from preclinical stage into the clinic), translatability (probability to be widely applied in the 'real world'), and (assumed) diagnostic quality. In our analysis, we show that most tracers are targeting PD-L1, PD-1, CTLA-4, and CD8 receptors by using antibodies or their fragments. Another finding is that plenty of tracers possess only minor iterations regarding chelators and nuclides instead of approaching the problem in a new innovative way. Based on the data, we suggest an orthogonal approach by targeting intracellular targets with PET-activatable small molecules that are currently underrepresented.
免疫疗法的应用已经彻底改变了某些癌症类型的治疗方案，但常规方法（如 CT/MRT 或 FDG PET-CT）和为化疗治疗开发的经典反应标准（如 RECIST 或 PERCIST）在评估反应方面变得困难重重。为了改善治疗反应评估和对患者人群进行分层，已经发表了大量新的示踪剂。我们收集了已发表示踪剂的信息（总共确定了 106 种单独的 SPECT/PET 示踪剂），并进行了基于描述符的分析；通过这种方式，我们根据目标选择、可开发性（从临床前阶段进入临床的可能性）、可转移性（在“真实世界”中广泛应用的可能性）和（假设）诊断质量对示踪剂进行分类。在我们的分析中，我们发现大多数示踪剂通过使用抗体或其片段来靶向 PD-L1、PD-1、CTLA-4 和 CD8 受体。另一个发现是，许多示踪剂在螯合剂和核素方面只有微小的迭代，而不是以新的创新方式解决问题。基于这些数据，我们建议采用一种基于 PET 激活的小分子的正交方法，这些小分子目前的代表性不足。
