Antibodies and fragments thereof are, because of high selectivity for their targets, considered as potential therapeutics and biomarkers for several neurological disorders. However, due to their large molecular size, antibodies/fragments do not easily penetrate into the brain. The aim of the present study was to improve the brain distribution via adsorptive-mediated transcytosis of an amyloid-beta (A beta) protofibril selective F(ab')(2) fragment (F(ab')(2)-h158). F(ab')(2)-h158 was cationized to different extents and the specific and unspecific binding was studied in vitro. Next, cationized F(ab')(2)-h158 was labelled with iodine-125 and its brain distribution and pharmacokinetics was studied in mice. Cationization did not alter the in vitro affinity to A beta protofibrils, but increased the unspecific binding somewhat. Ex vivo experiments revealed a doubling of brain concentrations compared with unmodified F(ab')(2)-h158 and in vivo imaging with single photon emission computed tomography (SPECT) showed that the cationized F(ab')(2)-h158, but not the unmodified F(ab')(2)-h158 could be visualized in the brain. To conclude, cationization is a means to increase brain concentrations of therapeutic antibodies or fragments and may facilitate the use of antibodies/fragments as imaging biomarkers in the brain. 2017 The Authors. Published by Elsevier Inc.