Synthesis and in vitro evaluation of [18F]fluoroethyl triazole labelled [Tyr3]octreotate analogues using click chemistry

A novel class of alkyne linked [Tyr3]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [18F]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reaction was observed for each alkyne analogue which has been investigated. Two lead alkyne linked [Tyr3]octreotate analogues, G-TOCA (3a) and βAG-TOCA (5a) have been identified to be highly reactive in the click reaction showing complete conversion to the [18F]2-fluoroethyl triazole linked [Tyr3]octreotate analogues FET-G-TOCA (3b) and FET-βAG-TOCA (5b) under mild conditions and with short synthesis times (5 min at 20 °C). As well as ease of synthesis, in vitro binding to the pancreatic tumour AR42J cells showed that both FET-G-TOCA and FET-βAG-TOCA have high affinity for the somatostatin receptor with IC50 of 4.0 ± 1.4, and 1.6 ± 0.2 nM, respectively.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide