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

Abstract

In mice bearing human breast cancer xenografts, we examined the biodistribution of 18F-fluorocyclophosphamide (18F-F-CP) to evaluate its potential as a noninvasive prognostic tool for predicting the resistance of tumors to cyclophosphamide therapy. Methods: 18F-F-CP was synthesized as we recently described, and PET data were acquired after administration of 18F-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 18F content in each tissue with a γ-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. 18F-F-CP uptake was highest in kidneys, lowest in brain, and intermediate in tumors, as determined by both image-based and tissue-based measurements. 18F-F-CP uptake was not inhibited by coadministration of an approximately x700 concentration of unlabeled cyclophosphamide. PET measures of 18F-F-CP uptake in tumor predicted the magnitude of the response to subsequent administration of cyclophosphamide. Conclusion: Noninvasive assessment of 18F-F-CP uptake using PET may potentially be helpful for predicting the response of breast tumors to cyclophosphamide before therapy begins. Copyright © 2007 by the Society of Nuclear Medicine, Inc.