PET Tracers Beyond FDG: Normal Variations and Benign Findings

The unique usefulness of PET lies in its ability to image the in vivo distribution and kinetics of a wide variety of biomolecules labeled with positronemitting radioisotopes. While [F-18]-FDG has been the workhorse of PET imaging, a number of other PET radiopharmaceuticals have been studied extensively in oncologic, cardiovascular, and neurologic disorders. These agents study biologic processes and molecular targets other than those involved in glucose metabolism, such as amino acid metabolism, purine and pyrimidine metabolism, cell turnover, receptors and transporters, abnormal protein deposition, bone turnover, and others. Newer approaches toward labeling of probes, image acquisition, and analysis and “fusion” of PET imaging with MRI have added extensive enthusiasm in the field. This issue of PET Clinics aims to review some of the extensively studied non-FDG PET radiopharmaceuticals with regard to their potential clinical usefulness, normal variations, benign findings, and pitfalls. The first article, by Antunovic and colleagues, emphasizes the need for, and provides an overview of, the ongoing efforts related to the standardization and quantification of non-FDG radiopharmaceuticals for PET imaging. Specific examples of [C-11] methionine and [C-11] choline are highlighted. The second article, by Singhal and colleagues, provides an overview of non-FDG PET radiopharmaceuticals used to assess various neurologic conditions, including dementia, movement disorders, epilepsy, brain tumors, and neuroinflammation. There is a renewed interest in [F-18] sodium fluoride bone imaging, likely due to the increasing availability of PET/CT scanners, improved logistics for the delivery of F-18-labeled radiotracers, and the higher quality images that can be acquired with PET/CT. The next two articles, written by Even-Sapir and Grant, review [F-18] sodium fluoride PET, focusing on adult and pediatric applications, respectively. The uptake of [F-18] choline is a marker of cellular proliferation and is potentially useful in several malignancies. Along with the physiologic uptake, benign variations, and effects of various treatments, the role of [F-18] choline is the subject of discussion in the article by Beheshti and colleagus. The article by Chondrogiannis and colleagues reviews [F-18] DOPA that was originally developed to study the integrity of the striatal dopaminergic system in the central nervous system but has additionally demonstrated efficacy for the evaluation of neuroendocrine tumors, brain tumors, and pancreatic cell hyperplasia. Radiolabeling of somatostatin receptor ligands with the generator-produced positron emitter gallium-68 using a chelator, such as DOTA, is an example of an alternate approach to labeling PET radiopharmaceuticals and has significantly advanced the field of somatostatin receptor imaging. The various Ga-68-labeled somatostatin receptor agents (DOTA-TOC, DOTA-NOC, and DOTATATE) are reviewed in the article by Ambrosini and colleagues. The following article by Herrmann and Buck reviews [F-18] fluorothymidine, a marker of cellular proliferation, with potential usefulness in a large number of oncologic conditions, including in the diagnosis and assessment of treatment response. [C-11] acetate is a biomarker for cell membrane lipid synthesis and also undergoes both catabolic and anabolic metabolism. Its use in various cardiologic and oncologic conditions and relevant variations and imaging pitfalls are reviewed in the article by Karanikas and Beheshti. PET/MRI using non-FDG PET ligands is an exciting, synergistic technology with relevance across medical and surgical subspecialties and is the subject of the review of the final article, by Pampaloni and Nardo. Overall, the current issue of the PET Clinics provides a comprehensive overview of some of the key aspects of PET imaging, with tracers beyond FDG, particularly their main clinical usefulness, normal variations, benign findings, and potential pitfalls. We hope that the readers will find this issue informative and useful, and that it will stimulate further research to enhance our understanding of pathophysiology of various diseases and to improve patient care. Finally, we would like to thank the authors for sharing their expertise and making a valuable contribution to the field.