Radiosyntheses using Fluorine-18: The Art and Science of Late Stage Fluorination

Abstract

Positron (β+) emission tomography (PE) is a powerful, noninvasive tool for the in vivo, three-dimensional imaging of physiological structures and biochemical pathways. The continued growth of PET imaging relies on a corresponding increase in access to radiopharmaceuticals (biologically active molecules labeled with short-lived radionuclides such as fluorine-18). This unique need to incorporate the short-lived fluorine-18 atom (t1/2 = 109.77 min) as late in the synthetic pathway as possible has made development of methodologies that enable rapid and efficient late stage fluorination an area of research within its own right. In this review we describe strategies for radiolabeling with fluorine-18, including classical fluorine-18 radiochemistry and emerging techniques for late stage fluorination reactions, as well as labeling technologies such as microfluidics and solid-phase radiochemistry. The utility of fluorine-18 labeled radiopharmaceuticals is showcased through recent applications of PET imaging in the healthcare, personalized medicine and drug discovery settings.

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

“…The development of new 18 F-based radiotracers remains an ongoing goal in the field of radiopharmacy and provides tools for specific cancer diagnostics using positron emission tomography (PET) [31–33]. When radiotracers are based on tumor-specific peptides, proteins or antibodies [34–35], mild and fast methods for radiolabeling are mandatory because of the short half-live of [ 18 F]fluoride ( t 1/2 : 110 min).…”

Fluorinated Nucleosides as an Important Class of Anticancer and Antiviral Agents

“…In addition, 18 F is also a low positron emission energy emitter giving a good spatial resolution for imaging. All these factors make it the optimal radioisotope for PET imaging and much effort has been put into the discovery of novel and efficient routes towards synthesis of novel 18 F-PET tracers [7][8] [9]. The glucose analogue 2-…”

“…is the most ubiquitous PET tracer with multiple applications in oncology, cardiology and neurology [9][10]. However, also many 18 Fnucleoside analogues are currently under clinical investigation as proliferation biomarkers, reporter imaging probes for personalised medicine and prediction tools of the response to nucleoside analogue chemotherapy [11].…”

Decarboxylative Fluorination Strategies for Accessing Medicinally- Relevant Products

“…Due to the large scope of substrates and operational simplicity, this transformation should facilitate the drug discovery process. For more details on PET imaging agents, the reader is referred to an alternate article [33]. …”