Development of ¹⁸F-fluorinatable dendrons and their application to cancer cell targeting

18F-fluorine is an ideal imaging PET (positron emission tomography) nuclide due to the low energy of its ß+ (positron) and pure ß+ decay. PAMAM dendrimers are branched organic molecules with multiple NH2 termini each of which can accommodate the attachment of functionalities. The presence of a thiol group also facilitates the conjugation of a targeting molecule. Here we describe the attachment of boroaryl moieties to the terminal NH2 groups of dendrimers and after cleavage of the bridging thiol group conjugation of the functionalized dendrons (half-dendrimers) to biotin. Incubation of the targeted, boroaryl-functionalized dendrons with 18F-fluoride in acetic acid facilitated their radiolabelling with a labelling efficiency of about 60%. We then demonstrated that the 18F-dendron-biotin bound to HER-2 expressing cells in-vitro pre-targeted with avidin-trastuzumab conjugate. The cell-associated 18F decreased with increasing dendron size suggesting that the larger dendrons sterically hindered binding of avidin with biotin. This is the first study to demonstrate that dendrimers can be functionalized with 18F-fluorinatable groups and used to target cell surface receptors.