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Biodistribution and Predictive Value of ¹⁸F-Fluorocyclophosphamide in Mice Bearing Human Breast Cancer Xenografts

¹ Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California; and ² Divison of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California

Correspondence: For correspondence contact: Daniel H.S. Silverman, MD, PhD, CHS AR-144, Nuclear Medicine Clinic, MC694215, UCLA Medical Center, Los Angeles, CA 90095-6942. E-mail: dsilver{at}ucla.edu

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 -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.

Key Words: ¹⁸F • cyclophosphamide • prognostic imaging • positron emission tomography • breast tumor therapy • breast cancer • small-animal imaging

Guest Editor: Kenneth A. Krohn, University of Washington Medical Center

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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