In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 635-635
Kurzfassung:
635 Background: About a third of HER2-overexpressing (HER2+) breast cancer pts will develop brain metastases in the course of their disease. Drug access to normal brain and brain metastases is therefore key to prevention and treatment of cerebral metastases. To provide direct evidence of Lap drug access and evaluate whether therapeutic doses of Lap act as a substrate for efflux transporters, thereby increasing Lap concentrations, we performed positron emission tomography (PET) studies with [ 11 C]Lap. Methods: Pts with HER2+ MBC with an ECOG of 〈 3 were grouped into 2 cohorts: with at least one 1-cm diameter brain metastasis or without brain metastases and underwent 90-minute dynamic cranial PET-CT scans after IV administration of a microdose ( 〈 1 mg) of [ 11 C]Lap before and after 8 days of oral Lap (1500 mg once daily). Arterial blood samples were performed to assess [ 11 C]Lap radioactivity contribution in blood and plasma, and the fraction of plasma [ 11 C] radioactivity corresponding to metabolites. Tissue time-radioactivity curves (TACs) were generated and [ 11 C]Lap exposure (AUC; area under TAC) derived for normal brain and brain metastases. Signal dissection of the total image activity was performed to remove the contribution of blood volume to the image and the actual tissue contribution due to [ 11 C]Lap obtained. Results: 6 pts (3 with brain metastasis) were recruited. Arterial plasma analysis revealed that [ 11 C]Lap contributed to 〉 80% of activity in plasma at 60 minutes. Tissue data revealed [ 11 C]Lap signal in normal brain was low with no appreciable uptake observed when corrected for blood volume contribution. [ 11 C]Lap uptake was higher in brain metastases compared with normal brain and appreciable, even after correction for tissue blood volume contribution. Uptake was also observed in extra-cranial normal tissue. There was no difference in [ 11 C]Lap uptake in normal brain and metastases between treatment-naïve and post-treatment scans. Conclusions: [ 11 C]Lap uptake in brain metastases was higher than in normal brain. [ 11 C]Lap drug access to brain metastases might therefore indicate possible efficacy against HER2+ brain metastases. Clinical trial information: NCT01290354.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.635
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2013
ZDB Id:
2005181-5
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