Nitrogen-13: historical review and future perspectives

Positron emission tomography is an ultra-sensitive, in vivo molecular imaging technique that allows the determination of the spatiotemporal distribution of a positron emitter labeled radiotracer after administration into living organisms. Among all existing positron emitters, (18) F has been by far the most widely used both in clinical diagnosis and in preclinical investigation, while the use of (11) C significantly increased after the 1980s because of the widespread installation of biomedical cyclotrons. The use of other shorter-lived positron emitters such as (13) N (T1/2  = 9.97 min) has been historically more restricted. Paradoxically, its stable isotope ((14) N) is present in many biological active molecules; consequently, the development of strategies for the efficient incorporation of (13) N into radiotracers would represent an interesting alternative to (11) C- and (18) F-labeling. In the current paper, the developments related to (13) N chemistry are reviewed, including different production routes of primary precursors and their applications to the preparation of more complex (13) N-labeled molecules. The current situation and future perspectives are also briefly discussed.