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Oxime formation between an aminooxy-functionalized peptide and an 18F-labelled aldehyde has recently been introduced as a powerful method for the rapid one-step chemoselective synthesis of radiofluorinated peptides. Here, the potential of using routinely produced and thus readily available [18F]fluorodeoxyglucose ([18F]FDG) as the aldehydic prosthetic group was investigated using an aminooxyacetyl-conjugated cyclic RGD peptide (cyclo(RGDfK(Aoa-(Boc)) as a model peptide. The use of [18F]FDG from routine production ([18F]FDGTUM) containing an excess of d-glucose did not allow the radiosynthesis of [18F]FDG-RGD in activities >37 MBq in reasonable yield, rendering the direct use of clinical grade [18F]FDG for the routine clinical synthesis of 18F-labelled peptides impossible. Using no-carrier-added (n.c.a.) [18F]FDG obtained via HPLC separation of [18F]FDGTUM from excess glucose, however, afforded [18F]FDG-RGD in yields of 56–93% (decay corrected) and activities up to 37 MBq. Suitable reaction conditions were 20 min at 120°C and pH 2.5, and a peptide concentration of 5 m M. In a preliminary in vivo biodistribution study in M21 melanoma-bearing nude mice, [18F]FDG-RGD showed increased tumour accumulation compared to the “gold standard” [18F]galacto-RGD (2.18 vs 1.49 %iD/g, respectively, at 120 min after injection), but also slightly increased uptake in non-target organs, leading to comparable tumour/organ ratios for both compounds. These data demonstrate that chemoselective 18F-labelling of aminooxy-functionalized peptides using n.c.a. [18F]FDG represents a radiofluorination/glycosylation strategy that allows preparation of 18F-labelled peptides in high yield with suitable pharmacokinetics. As soon as the necessary n.c.a. preparation of [18F]FDG prior to reaction with the Aoa-peptide can be implemented in a fully automated [18F]FDG-synthesis, [18F]fluoroglucosylation of peptides may represent a promising alternative to currently used chemoselective one-step 18F-labelling protocols. [ABSTRACT FROM AUTHOR]

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50–500 μm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [18F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, μ-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the 18F-labelled intermediate followed by on-line formulation of [18F]FDG. In-capillary18F-fluorination of 2.1 μmol 1,3,4,6-tetra- O-acetyl-2- O-trifluoromethanesulphonyl-beta- d-mannopyranose (TATM; precursor for [18F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40°C resulted in a radiochemical yield of 88 ± 4% within <7 min. Reproducibility, robustness and suitability as a fast and efficient radiopharmaceutical research tool for 18F-fluorination was demonstrated by eight independent, sequentially performed ICRs which provided identical tracer quality (radiochemical purity >97%, MeCN <5 μg/ml) and similar absolute yields (approximately 1.4 GBq). The described ICR process is a simple and efficient alternative to classic radiotracer production systems and provides a comparatively cheap instrumental methodology for the repetitive production of [18F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that similar or nearly identical procedures, and thus instrumentation, will allow ICR of other 18F-labelled radiopharmaceuticals. [ABSTRACT FROM AUTHOR]