SUMMARY:

Positron Emission Tomography (PET) is a unique tool for the investigation, localization, and quantification of physiological activities in vivo by tracing the involved and accompanying biochemical processes. Because of its nuclear and chemical properties, fluorine-18, which is commonly produced by a cyclotron using the ¹⁸O(p,n) ¹⁸F or the ²⁰Ne(d, ?) ¹⁸F nuclear process, is a nearly ideal positron emitting radionuclide. Its half-life of 109.7 min permits tracer synthesis and imaging protocols extending over hours and allows distribution of ¹⁸F-radiopharmaceuticals to hospitals and facilities lacking a cyclotron. The low maximum positron energy of 635 keV results in low radiation doses, short ranges in tissue and excellent imaging resolution. Introduction of ¹⁸F-fluorine, either via nucleophilic strategies using [ ¹⁸F]F ^? or electrophilic routes using molecular [ ¹⁸F]F ₂, permits the synthesis of a broad spectrum of compounds within a time compatible with the half-life. Although fluorine is only slightly larger than a hydrogen atom, changes in the physiological behavior of bioactive compounds as a result of alteration in metabolic stability, lipophilicity, affinity to the target or other structures etc. are often observed even after F-for-H or F-for-OH substitutions. In this chapter an overview of the scope and limitations of the ¹⁸F-chemistry is given. Fluorination strategies, routes and synthetic aspects are exemplified, as far as possible, by established and selected ¹⁸F-radiopharmaceuticals with...