Biodistribution and Predictive Value of 18F-Fluorocyclophosphamide in Mice Bearing Human Breast Cancer Xenografts
Amanda L. Kesner 1,
Wei-Ann Hsueh 1,
Nwe Linn Htet 1,
Betty S. Pio 1,
Johannes Czernin 1,
Mark D. Pegram 2,
Michael E. Phelps 1,
and
Daniel H.S. Silverman 1*
1 Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
2 Divison of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California
* To whom correspondence should be addressed. E-mail: dsilver{at}ucla.edu.
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Abstract |
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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
