Radiohalogen incorporation into organic systems

Abstract

SummaryThis Review reports the more recent applications of radiohalogen labelling in organic compounds. Modern synthetic methods place more emphasis upon substitution at specific sites. Electrophilic substitution, especially at aromatic carbon atoms, involves displacement of halogen or of metals rather than the earlier popular halogen-deprotiation processes. Nucleophilic displacement, at either aliphatic or aromatic sites, has also become widespread since it may be made more selective by the inclusion of appropriate activating groups or suitable displaced groups. Microwave and thermally induced methods are both reported with a critical assessment of the value of each process.

18F‐Labeling of Peptides by means of an Organosilicon‐Based Fluoride Acceptor

“…This exchange reaction is remarkably fast and exceeds the RCY of 50-70 % usually obtained by nucleophilic 18 F-19 F substitution of activated aromatic compounds, which normally requires high reaction temperatures and HPLC purification. [13,14] The specific activity obtained is competitive with clinically used radiotracers, which show specific activities between 100-1000 GBq mmol À1 . As a result of the very mild reaction conditions, a noteworthy advantage of the SiFA method is the exclusive formation of product 3 (Figure 3).…”

Highly efficient click labeling using 2-[18F]fluoroethyl azide and synthesis of an 18FN-hydroxysuccinimide ester as conjugation agent

“…Fluorine-18, which is readily available in high specific activity from most medical cyclotrons, is widely used for PET radiolabeling of small molecules because of its small size and favorable decay characteristics (100% positron, t 1/2 = 109.7 min). Typical fluorine-18 radiolabeling employs nucleophilic substitution of a good leaving group with [ 18 F]fluoride, which is produced in [ 18 O]water and azeotropically dried in the presence of Kryptofix 222 and potassium carbonate or another base at elevated temperatures [3, 4]. Because this reaction proceeds under harsh and basic conditions, attempts to label temperature- or base-sensitive products may result in a lot of radiolabeled and non-radioactive by-products, poor yields, and high variability.…”

18F‐Markierung von Peptiden mithilfe eines Organosilicium‐Fluoridacceptors

“…Speziell für Peptide, die bislang nur durch komplexe, vielstufige Prozesse radioaktiv markiert werden konnten, ist die Entwicklung einfacher Markierungsreaktionen entscheidend. [4] Als Alternative zu den herkömmlichen 18 [13,14] Die spezifische Aktivität des Produkts liegt im Bereich der spezifischen Aktivitäten klinisch verwendeter Radiotracer (100-1000 GBq mmol À1 ).…”

“…[9] Im Zuge der Untersuchungen wurden zunächst drei [ 18 Um Organosilane zur 18 F-Markierung von Peptiden für die Tumordiagnostik [12] zu nutzen, müssen die Kupplungsschritte der Markierungsstrategie schnell verlaufen, denn die Halbwertszeit von 18 19 F-Substitutionen von aktivierten Arenen bei hoher Temperatur mit anschließender HPLC-Aufreinigung erhalten werden. [13,14] Die spezifische Aktivität des Produkts liegt im Bereich der spezifischen Aktivitäten klinisch verwendeter Radiotracer (100-1000 GBq mmol À1 ). [1] Als Folge der milden Reaktionsbedingungen entstehen bei der SiFA-Methode keinerlei radioaktive Nebenprodukte.…”