Brain molecular imaging with positron emission tomography (PET) has been utilized for clinical study, diagnosis and drug development of neurodegenerative diseases. However, further development of typically used ¹⁸F-labeled small compounds have been troubled by non-specific binding and low affinity against target molecules. Hence, protein binders like antibodies or their derivatives have attracted interest with their high specificity and affinity. However, their large molecular size and small entry into the brain remain challenges for clinical application. In the present study, we use a brain shuttle peptide concept for protein brain delivery and evaluate the pharmacokinetics of a blood-brain barrier-permeable small-size protein affinity ligand ([¹⁸F]AS69-ApoE). We found that [¹⁸F]AS69-ApoE showed higher brain accumulation than its original ([¹⁸F]AS69) at 10-min and 30-min post injection; on the other hand, [¹⁸F]AS69-ApoE was cleared from brain at 120-min post injection. Moreover, in vitro and in vivo stability analyses showed that these protein tracers are mostly stable in mouse plasma. These results imply the possibility of small-size protein binders for molecular brain PET imaging.