The development of brain imaging agents is often challenging. Good BBB permeability, acceptable nondisplaceable binding, or sufficient metabolic stability are only some of the criteria that must be met. Multiple trade-offs between parameters that influence these criteria exist. For example, high lipophilicity increases brain uptake, but also its non-displaceable binding component. It is, therefore, essential to identify the right value for these parameters, i.e., the value that positively effects one criterion without disturbing another one. Nowadays, many physicochemical parameters can simply be estimated from their chemical structure. These estimations can be used to calculate a variety of composite scores. The CNS MPO and BBB scores, for example, are based on parameters such as MW, numbers of H-bond donors/acceptors, clogD7.4 or clogP. These scores can be used to estimate the probability of a certain structure to enter the brain and be used as a brain tracer consequently. In this work, we carefully designed a set of 18 Tzs, which are predicted to be suitable brain imaging agents. According to the PET MPO and BBB score, they possess a probability of >75% to enter the brain (Figure ). Designed Tzs possess a rate constant (k2) of >70,000 M -1 s -1 in PBS with "standard" TCO. We have recently shown that such rate constants increase drastically the in vivo click performance of Tzs for pretargeting. As typical brain target concentrations are in the order of 100 nM, aforementioned rate constants will also be sufficient for pretargeted imaging beyond the BBB (SI).