Editorial [Hot Topic: PET Tracers Based on Nonstandard Radionuclides (Guest Editor: Weibo Cai)]

Molecular imaging, in particular positron emission tomography (PET), plays pivotal roles in 21st century personalized medicine. PET has been used in the clinic for decades and 18F-FDG has become indispensible in many facets of patient management, such as cancer staging and treatment monitoring. Commonly used PET tracers are typically labeled with 15O (t1/2: 122.2 s), 13N (t1/2: 10.0 min), 11C (t1/2: 20.4 min), or 18F (t1/2: 109.7 min). Driven by the ever-increasing availability of preclinical/ clinical PET scanners and radioisotopes, research on nonstandard PET nuclides has flourished over the last decade. Since the abovementioned four standard radionuclides all have relatively short half-lives, a wide variety of nonstandard radionuclides (typically with half-lives in the order of hours to days) have been explored for labeling larger molecules to interrogate a variety of biological events through PET imaging. This special issue of Current Radiopharmaceuticals is focused on the PET tracers based on nonstandard radionuclides. In the first article of this issue, Dr. Tolmachev gave a comprehensive overview on the use of two positron-emitting isotopes of bromine, 75Br (t1/2: 96.7 min) and 76Br (t1/2: 16.2 h), for PET imaging applications. Next, Dr. Wuest and co-workers provided a thorough survey on applications of 94mTc-based PET, where the production/processing of 94mTc (t1/2: 52.5 min) and its coordination chemistry were both described in detail. Dr. Nickles and co-workers discussed in depth about the unrealized potential of 34mCl (t1/2: 32.2 min) for PET imaging. Recent improvements in accelerator targetry have made radiochlorine available from small cyclotrons, which can be used for the synthesis of novel imaging probes through both electrophilic and nucleophilic avenues. In the next review, Dr. Sun and co-workers summarized the recent advances in copper radiopharmaceuticals, which are composed of five radioisotopes: 60Cu (t1/2: 23.7 min), 61Cu (t1/2: 3.4 h), 62Cu (t1/2: 9.9 min), 64Cu (t1/2: 12.7 h), and 67Cu (t1/2: 2.6 d). Due to the availability and production cost, the research efforts in copper radiopharmaceuticals are mainly focused on the use of 64Cu, which has low positron energy thus is ideal for PET imaging quantification. The article by Dr. Liu and co-workers is an excellent summary on 86Y (t1/2: 14.7 h)-based PET tracers, which have gained increasing attention since they are ideal surrogates for in vivo determination of biodistribution and dosimetry of therapeutic 90Y (pure β emitter; t1/2: 2.7 d)-based radiopharmaceuticals. Lastly, the current status of PET imaging with 89Zr (t1/2: 3.3 d) was described by Dr. Cai and co-workers. With decay half-life well matched to the circulation half-lives of antibodies, 89Zr has been extensively studied over the last decade and successful pilot studies in cancer patients have already been reported. Initially, I intended to also cover a few other nonstandard radionuclides in this special issue, such as 55Co (t1/2: 17.5 h), 68Ga (t1/2: 67.7 min), 82Rb (t1/2: 75.0 s), 124I (t1/2: 4.2 d), arsenic isotopes, among others. However, many of the experts that were invited were not able to contribute due to their tight schedule and various other commitments. With more and more promising PET tracers being developed using nonstandard radionuclides, clinical translation is key. Over the last decade, the field of molecular imaging has witnessed tremendous expansion. The next decade of the 21st century will likely see more and more nonstandard radionuclide-based PET tracers enter clinical trials and benefit cancer patients, which will usher in a brand new era of PET imaging beyond 18F-FDG.