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Eur J Nucl Med Mol Imaging. 2009 Mar;36(3):406-12. doi: 10.1007/s00259-008-1010-z. Epub 2008 Dec 18.

Noninvasive functional imaging of P-glycoprotein-mediated doxorubicin resistance in a mouse model of hereditary breast cancer to predict response, and assign P-gp inhibitor sensitivity.

Author information

1
Department of Radiology and Nuclear Medicine, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands. fw.v.leeuwen@nki.nl

Abstract

PURPOSE:

Using a "spontaneous" mammary mouse tumor model we set out to develop diagnostic approaches for non-invasive P-glycoprotein (P-gp) staging and response prediction.

METHODS:

(99m)Tc-MIBI efflux rates were measured using a gamma camera in three Brca1 (-/-); p53 (-/-) mouse mammary tumors that have different Mdr1a/b expression levels. The efflux rates were quantified in the 10-30-min period after injection. In addition to the P-gp-mediated efflux measurements in untreated tumors, efflux measurements were performed in the presence of the P-gp inhibitor tariquidar. Volumetric doxorubicin response patterns for the different tumors were determined and correlated with the efflux rates.

RESULTS:

Combined pre- and post-inhibitor treatment imaging of P-gp-mediated efflux correlated with Mdr1a/b expression: basal (0.0026, p = 0.16), 3-fold Mdr1a/b (0.0074, p = 0.02), and 17-fold Mdr1a and 46-fold Mdr1b (0.012, p = 0.002). Based on the doxorubicin response of these tumors, we generated a computer-aided diagnosis model that predicts the likelihood of drug resistance.

CONCLUSIONS:

Quantified (99m)Tc-MIBI efflux has potential to: (1) noninvasively assign Mdr1 expression levels, (2) predict the therapeutic impact of a P-gp inhibitor, and (3) noninvasively assess the probability of drug resistance.

PMID:
19093112
DOI:
10.1007/s00259-008-1010-z
[Indexed for MEDLINE]

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