Fig. 1.

Limited trastuzumab access to metastases of the brain. MDA-MB-231-BR-HER2 cells were implanted by intra-cardiac injection and grew as metastases in the brains and liver of NOD/SCID mice. Mice were treated with 5 mg/kg trastuzumab and tissues collected at 3 h. Fluorescent images of stained cryosections are inverted and shown in grey scale for Hoechst 33342 nuclear dye, HER2 receptor and bound trastuzumab, and all are overlaid in a false color image. Smaller brain micro-metastases (rows 1–3) ranging from small clusters of a few cells to 150 µm in maximum diameter had no detectable bound trastuzumab on the HER2-positive tissues. The largest HER2-positive brain lesion found (row 4) is > 1.5 mm in maximum diameter, and is the only lesion found in the brain with delivered, bound trastuzumab in a heterogeneous pattern. An example metastatic lesion in the liver (row 5) has trastuzumab access from the outside, distributing towards the centre. All scale bars 150 µm. (Color figure online)