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

In terms of nuclear decay F-18 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 (TM)-biotin facilitates the application of short-lived nuclides by their attachment to biotin for imaging cell surface proteins targeted with Neutravidin (TM)-conjugated antibodies. Methods: Boroaryl functionalised biotin was prepared with a PEG linker and radiolabelled by incubation with F-18 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 (TM)-conjugated trastuzumab, washed, and then incubated with F-18-PEG-biotin. Results: The F-18-fluorination of boroaryl-PEG-biotin was much more efficient than reported for other versions of boroaryl-biotin. The novel F-18-PEG-biotin was demonstrated to bind to HER-2-expressing cells in-vitro pre-incubated with Neutravidin (TM)-conjugated trastuzumab. Conclusion: Biotin can be functionalised with boroaryl and readily F-18-radiolabelled in aqueous solution and will bind to cells pre-incubated with Neutravidin (TM)-antibody conjugates. (C) 2011 Elsevier Ltd. All rights reserved.