18F -PEG-biotin: Precursor (boroaryl-PEG-biotin) synthesis, 18F -labelling and an in-vitro assessment of its binding with Neutravidin™-trastuzumab pre-treated cells.

Abstract In terms of nuclear decay 18 F is the most ideal PET nuclide but its short t 1/2 precludes its use for directly labelling whole antibodies due to their long blood residence times. Pre-targeted imaging using affinity systems such as Neutravidin™–biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin™-conjugated antibodies. Methods Boroaryl functionalised biotin was prepared with a PEG linker and radiolabelled by incubation with 18 F in acidified aqueous solution. Cells expressing high (SKBr3), medium (MDA-MB-453) and low (MDA-MB-468) levels of HER-2 were pre-incubated with Neutravidin™-conjugated trastuzumab, washed, and then incubated with 18 F-PEG-biotin. Results The 18 F-fluorination of boroaryl-PEG-biotin was much more efficient than reported for other versions of boroaryl-biotin. The novel 18 F-PEG-biotin was demonstrated to bind to HER-2-expressing cells in-vitro pre-incubated with Neutravidin™-conjugated trastuzumab. Conclusion Biotin can be functionalised with boroaryl and readily 18 F-radiolabelled in aqueous solution and will bind to cells pre-incubated with Neutravidin™–antibody conjugates.