Automated Synthesis Of The Generic Peptide Labelling Agent N-Succinimidyl 4-[F-18]Fluorobenzoate And Application To F-18-Label The Vasoactive Transmitter Urotensin-Ii As A Ligand For Positron Emission Tomography

Introduction: The objectives were the work were to develop an automated production N-succinimidyl 4-[F-18]fluorobenzoate ([F-18]-SFB) and to test whether the vasoactive peptide urotensin-II (U-II) could be labelled by conjucation with [F-18]-SFB.Methods: A TRACERlab MXFAG sythesizer including an HPLC unit was used. The MS Excel synthesis sequence and the standard disposable FDG cassette were modified to allow the synthesis of [F-18]-SFB. U-II was subsequently conjugated with [F-18]-SFB, and the resulting F-18-labelled peptides were characterised using in vitro ligand binding assays.Results: [F-18]-SFB was successfully synthesised in the TRACERlab MXFDG in 44.3 +/- 2.5% (n=25) radiochemical yield in 98 min. [F-18]-SFB (8-12 GBq) has been produced with specific activities in the range of 250-350 GBq/mu mol and a radiochemical purity >95%. [F-18]-SFB was subsequently used to label U-II. Two radiolabelled products, [F-18]-(Glu(I))-U-II and [F-18]-(Lys(8))-U-II, were formed in an isolated radiochemical yield from [F-18]-SFB of 5.2 +/- 0.3% and 29.0 +/- 3.7%, respectively (n=7). Radioligand binding assays revealed that [F-18]-(Glu(I))-U-II had retained subnanomolar affinity. Binding to human skeletal muscle (n=3) was concentration dependent and saturable with K-d=0.84+/-0.51 nM, B-max = 0.69 +/- 0.14 fmol/mg protein and Hill slope (nH)=1.03+/-0.12.Conclusions: [F-18]-SFB has been synthesised using the TRACERlab MXFDG module, allowing production of up to 8-12 GBq of [F-18]-SFB with specific activities of 250-350 GBq/mu mol. [F-18]-SFB was used for the labelling of U-II. In vitro characterisation demonstrated that [F-18]-(Glu(I))-U-II had retained desirable binding properties and may be suitable as a positron emmission tomography radioligand for the imaging of the U-II receptor. (C) 2008 Elsevier Inc. All rights reserved.