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 β+ (positron) and pure β+ 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 the 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.