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J Nucl Med. 2007 Dec;48(12):2021-7. Epub 2007 Nov 15.

Biodistribution and predictive value of 18F-fluorocyclophosphamide in mice bearing human breast cancer xenografts.

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1
Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-6942, USA.

Abstract

In mice bearing human breast cancer xenografts, we examined the biodistribution of (18)F-fluorocyclophosphamide ((18)F-F-CP) to evaluate its potential as a noninvasive prognostic tool for predicting the resistance of tumors to cyclophosphamide therapy.

METHODS:

(18)F-F-CP was synthesized as we recently described, and PET data were acquired after administration of (18)F-F-CP in mice bearing human breast cancer xenografts (MCF-7 cells). Tracer biodistribution in reconstructed images was quantified by region-of-interest analysis. Distribution was also assessed by harvesting dissected organs, tumors, and blood, determining (18)F content in each tissue with a gamma-well counter. The mice were subsequently treated with cyclophosphamide, and tumor size was monitored for at least 3 wk after chemotherapy administration.

RESULTS:

The distribution of harvested activity correlated strongly with distribution observed in PET images. Target organs were related to routes of metabolism and excretion. (18)F-F-CP uptake was highest in kidneys, lowest in brain, and intermediate in tumors, as determined by both image-based and tissue-based measurements. (18)F-F-CP uptake was not inhibited by coadministration of an approximately x700 concentration of unlabeled cyclophosphamide. PET measures of (18)F-F-CP uptake in tumor predicted the magnitude of the response to subsequent administration of cyclophosphamide.

CONCLUSION:

Noninvasive assessment of (18)F-F-CP uptake using PET may potentially be helpful for predicting the response of breast tumors to cyclophosphamide before therapy begins.

PMID:
18006620
DOI:
10.2967/jnumed.107.045716
[Indexed for MEDLINE]
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