Sutherland Andrew, Dweck Marc R, Newby David E, Tavares Adriana A S
School of Chemistry, University of Glasgow, Glasgow, United Kingdom.
British Heart Foundation-University of Edinburgh Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
Pharmacol Rev. 2025 Jul;77(4):100066. doi: 10.1016/j.pharmr.2025.100066. Epub 2025 May 15.
The development of the first total-body positron emission tomography (PET) clinical scanner is a transformational moment in nuclear medicine, reigniting the field by tackling 2 long-standing and critical barriers to the widespread clinical use of PET: radiation dose and patient throughput. Total-body PET also provides several other unique research and clinical opportunities, including potential to streamline radiotracer discovery and development pipelines. PET does not exist without radiotracers. However, despite decades of radiotracer development programs, the number of successful PET radiotracers adopted and approved for human use is extremely low. In neurology, an important area for nuclear medicine, only approximately 4% of all novel radiotracers that survive the radiotracer translational "valley of death" are adopted clinically. The potential for total-body PET technology to reverse these low numbers of radiotracer development and adoption is high. This will require the PET community to come together with the regulators to chart new frameworks for radiotracer development and translational pipelines. This article will discuss which stages of the radiotracer discovery pipeline can benefit most from the recent development of total-body PET technology. It will review the latest key developments in radiochemistry modernization and describe how these could ameliorate regulatory hurdles and deliver the groundbreaking potential of total-body PET. Finally, this article will highlight emerging radiotracer discovery opportunities that could be rapidly facilitated by total-body PET. SIGNIFICANCE STATEMENT: In addition to creating new opportunities for clinical research and patient care, total-body positron emission tomography technology can also embolden radiochemistry modernization in the clinic and break long-standing translational barriers encountered during radiotracer discovery pipelines.
首台全身正电子发射断层扫描（PET）临床扫描仪的问世是核医学领域的一个变革性时刻，通过攻克PET在临床广泛应用中存在的两个长期且关键的障碍——辐射剂量和患者通量，为该领域注入了新的活力。全身PET还提供了其他一些独特的研究和临床机遇，包括简化放射性示踪剂发现与开发流程的潜力。没有放射性示踪剂就没有PET。然而，尽管经过了数十年的放射性示踪剂开发项目，但被采用并批准用于人体的成功PET放射性示踪剂数量极低。在核医学的一个重要领域——神经学中，在放射性示踪剂转化的“死亡谷”中存活下来的所有新型放射性示踪剂中，只有约4%被临床采用。全身PET技术扭转放射性示踪剂开发和采用数量低迷状况的潜力很大。这将需要PET领域与监管机构共同努力，制定放射性示踪剂开发和转化流程的新框架。本文将讨论放射性示踪剂发现流程的哪些阶段能从全身PET技术的最新发展中获益最多。它将回顾放射化学现代化的最新关键进展，并描述这些进展如何能够缓解监管障碍，释放全身PET的突破性潜力。最后，本文将重点介绍全身PET能够迅速推动的新兴放射性示踪剂发现机遇。意义声明：除了为临床研究和患者护理创造新机遇外，全身正电子发射断层扫描技术还能推动临床放射化学现代化，打破放射性示踪剂发现流程中遇到的长期转化障碍。
