Ex vivo biodistribution of radiolabeled anti-HER2 tracers in brain tumor-bearing mice. (A) Ex vivo biodistribution analyses of [111In]-labeled compounds in HER2pos tumor-bearing mice, at 1 h p.i. (sdAbs) and 3 d p.i. (mAb) (n = 4). For sdAbs only kidneys show elevated uptake, whereas trastuzumab has increased tracer uptake in all highly vascularized organs. Detail of tracer uptake in tumor, brain and blood shows a significantly higher tumor uptake for [111In]-2Rs15d in (B) SKOV3.IP1 and (C) 231Br brain tumors compared to the non-targeting [111In]-R3B23. Increased tumor-to-brain ratio of [111In]-trastuzumab was only observed in 231Br tumors (C). (ns: not significant, ** p < 0.01, *** p < 0.005, **** p < 0.001).