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EJNMMI Research
Published in: EJNMMI Research 1/2015

Open Access 01-12-2015 | Original research

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

Authors: Azeem Saleem, Graham E Searle, Laura M Kenny, Mickael Huiban, Kasia Kozlowski, Adam D Waldman, Laura Woodley, Carlo Palmieri, Charles Lowdell, Tomomi Kaneko, Philip S Murphy, Mike R Lau, Eric O Aboagye, Raoul C Coombes

Published in: EJNMMI Research | Issue 1/2015

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Abstract

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 ([11C]lapatinib)-PET. Less than 20 μg of [11C]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 [11C]lapatinib after 60 min. PET signal in the brain corresponded to circulating radioactivity levels, with no [11C]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 [11C]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
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Metadata
Title
Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer
Authors
Azeem Saleem
Graham E Searle
Laura M Kenny
Mickael Huiban
Kasia Kozlowski
Adam D Waldman
Laura Woodley
Carlo Palmieri
Charles Lowdell
Tomomi Kaneko
Philip S Murphy
Mike R Lau
Eric O Aboagye
Raoul C Coombes
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-015-0103-5

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