We investigated structure-activity relationships of a library of 18 different 18 F-Tzs, their in vitro imaging contrast and in vivo brain pharmacokinetics to predict their in vivo click performance on targets beyond the BBB. No clear relation could be identified. However, slow metabolism as well as high lipophilicity appear to beneficial for high brain uptake. [ 18 F]18 showed the best imaging properties. High brain uptake combined with good imaging contrast are the key properties of this tracer to be our prime candidate to be used in further pretargeted imaging studies beyond the BBB (Figure ). In a next step, we will design BBB penetrating and TCO-modified mAbs that can be targeted and imaged with [ 18 F]18. This possibility will ultimately enable pretargeted imaging of brain targets, such as protein isoforms, which can currently not be imaged.