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Background  Brain metastases are common in human epidermal growth factor receptor (Her)-2-positive breast cancer. Drug access to brain metastases and normal brain is key to management of cranial disease. In this study, positron emission tomography (PET) scanning after administration of radiolabelled lapatinib was used to obtain direct evidence of cranial drug access.    Methods  Patients with Her-2+ metastatic breast cancer either with at least one 1-cm diameter brain metastasis or without brain metastases underwent dynamic carbon-11 radiolabelled lapatinib ([ 11 C]lapatinib)-PET. Less than 20 μg of [ 11 C]lapatinib was administered before and after 8 days of oral lapatinib (1,500 mg once daily). Radial arterial blood sampling was performed throughout the 90-min scan. The contribution of blood volume activity to the tissue signal was excluded to calculate lapatinib uptake in normal brain and metastases. Partitioning of radioactivity between plasma and tissue ( V   T ) was calculated and the tissue concentration of lapatinib derived. Plasma lapatinib levels were measured and adverse events noted.    Results  Six patients (three with brain metastases) were recruited. About 80% plasma radioactivity corresponded to intact [ 11 C]lapatinib after 60 min. PET signal in the brain corresponded to circulating radioactivity levels, with no [ 11 C]lapatinib uptake observed in normal brain tissue. In contrast, radioactivity uptake in cranial metastases was significantly higher ( p  = 0.002) than that could be accounted by circulating radioactivity levels, consistent with [ 11 C]lapatinib uptake in brain metastases. There was no difference in lapatinib uptake between the baseline and day 8 scans, suggesting no effect of increased drug access by inhibition of the drug efflux proteins by therapeutic doses of lapatinib.    Conclusions  Increased lapatinib uptake was observed in brain metastases but not in normal brain.    Trial registration  ClinicalTrials.gov:  NCT01290354

Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer