title: Synthesis and in vitro evaluation of [18F]fluoroethyl triazole labelled [Tyr3]octreotate analogues using click chemistry.
abstract: A novel class of alkyne linked [Tyr(3)]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [(18)F]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 [Tyr(3)]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 [(18)F]2-fluoroethyl triazole linked [Tyr(3)]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 IC(50) of 4.0±1.4, and 1.6±0.2 nM, respectively.
authors: GE Healthcare, MDx Discovery, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors: Lisa
authors: L
authors: Iddon
authors: Julius
authors: J
authors: Leyton
authors: Bård
authors: B
authors: Indrevoll
authors: Matthias
authors: M
authors: Glaser
authors: Edward G
authors: EG
authors: Robins
authors: Andrew J T
authors: AJ
authors: George
authors: Alan
authors: A
authors: Cuthbertson
authors: Sajinder Kaur
authors: SK
authors: Luthra
authors: Eric O
authors: EO
authors: Aboagye
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D005462:Fluorine Radioisotopes / Q000737:chemistry; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D005462:Fluorine Radioisotopes; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D014230:Triazoles; C470036:octreotate, Tyr(3)-; D003300:Copper